Start vom Kosmodrom Baikonur; Landung 95 km nördöstlich von Arkalyk.

Hauptaufgabe der Mission war es, die ISS-Expedition 9 zur Raumstation zu bringen. Die Mannschaft wurde als "Caretaker"-Crew bezeichnet. Nach zweitägigem Alleinflug koppelte Sojus TMA-4 am 21.April 2004 an die ISS an. Gennadi Padalka und Michael Fincke bildeten die neue ISS-Stammbesatzung. Zunächst führte André Kuipers Forschungsarbeiten im Rahmen des europäischen Programms Delta durch. Die Stammbesatzung führte insgesamt 21 Experimente und vier Weltraumspaziergänge durch.

Die EVA 1 durch Gennadi Padalka und Michael Fincke am 24. Juni 2004 musste nach 14 Minuten abgebrochen werden, weil massive Druckverluste bei Finckes Orlan-Raumanzug auftraten. Geplant war eine EVA von 6 Stunden.

Die zweite EVA unternahmen Gennadi Padalka und Michael Fincke am 30. Juni 2004 (5h 40min) zur Installation eines neuen Stromkreisunterbrechers zur Wiederherstellung der Stromverbindung zu einem von vier Gyroscopen (Orientierung des Komplexes). Außerdem wurden zwei flexible Handläufe und die Endstücke zweier weiterer Handläufe angebracht und ein Monitor montiert, der Verunreinigungen an der Außenhaut der Station messen soll.

Die dritte EVA wurde ebenfalls durch Gennadi Padalka und Michael Fincke am 03. August 2004 (4h 30min) ausgeführt. Sie diente dem Austausch mehrerer Material-Experimente und eines Überwachungsgerätes, zur Triebwerks-Verschmutzung, Installation von Reflektoren und Kommunikations-Ausrüstung für die Ankopplung eines neuen Transportschiffes der ESA, das in 2005 ankoppelte.

Die vierte und letzte EVA durch Gennadi Padalka und Michael Fincke erfolgte am 03. September 2004 (5h 21m) zur Installation von drei Antennen an der Außenseite des Swesda-Moduls, zur Unterstützung der automatischen Ankopplung eines neuen Versorgungs-Raumschiffs, des European Automated Transfer Vehicle, Ersetzen eines Pumpen-Paneels am Sarja-Modul, Installation von Führungsleisten, zur Befestigung von Raumanzügen an den Griffen von Sarja, Installation von Handgriff-Sicherungen nahe der Luke am Pirs Docking Compartment.

Während ihres Aufenthaltes an Bord der ISS führte die Crew der Expedition 9 folgende wissenschaftlichen Experimente durch (vollständige Auflistung):
Actin (Role of Weightlessness on Metabolism),
ADUM (Advanced Diagnostic Ultrasound in Microgravity),
ARISS (Amateur Radio on the International Space Station),
BCAT-3-4-CP (Binary Colloidal Alloy Test - 3 and 4: Critical Point),
BCAT-3-SC (Binary Colloidal Alloy Test - 3: Surface Crystallization),
Biodegradation (Initial stage of Biodegradation and Biodeterioration in Space),
Bioekologia (Generation of High Efficiency of Microorganisms for the Production of Preparations of Biodegradable Oil, Organophosphorus Material, Measures for the Protection of Plants, as well as, of Exopolysaddharides Uses in the Petroleum Industry),
Biopsy (Effect of Prolonged Space Flight on Human Skeletal Muscle),
Biorisk (Influence of Factors of the Space Environment on the Condition of the System of Microorganisms-Hosts Relating to the Problem of Environmental Safety of Flight Techniques and Planetary Quarantine),
Biotest (Biochemical Status of Humans in Long Duration Space Flight),
Brados (Acquisition of Data About the Radiological, Electromagnetic and Different Physical Environments on Board ISS, and Their Effects on the Safety of the Crew, Space Equipment and Materials),
Cardio-ODNT (Dynamics of the Main Factors of Cardiac Function, of Central and Regional Circulation in Rest and During the Influence of Lower Body Negative Pressure),
CEO (Crew Earth Observations),
CFE (Capillary Flow Experiment),
Clinical Nutrition Assessment (Clinical Nutrition Assessment of ISS Astronauts, SMO-016E),
Conjugation (Development of Methods for Designing New Recombinants Producing Strains of Bacteria in Space Flight),
Diatomeya (Stability of Geographical Position and Configuration of Borders of Bioproductive Water Zones of the World Oceans, Observations by Orbition Station Crews),
Diurez (Fluid and Electrolyte Metabolism and Hormonal Regulaltion of Fluid Volume),
EarthKAM (Earth Knowledge Acquired by Middle School Students),
Ekon (Experimental Survey on Evaluating the Possibility of Using th Russian Segment of ISS for Environmental Inspection of Work Areas of Various Facilities (Features)),
Environmental Monitoring (Environmental Monitoring of the International Space Station),
EPO (Education Payload Operations),
EPO-Demos (Education Payload Operation - Demonstrations),
ETD (Eye Tracking Device),
Farma (Characteristics of Pharmacological Responses (absorption, distribution and elimination of acetominophene) in Long Duration Space Flight),
FMVM (Fluid Merging Viscosity Measurement),
Foam (Viscous Liquid Foam - Bulk Metallic Glass),
Gematologia (Morphofunctional Characteristic of Blood Cells and the Intensity of Erythropoiesis in Humans by the Influence of Factors of Space Flight),
Heart (Physiological Parameters that Predict Orthostatic Intolerance After Spaceflight),
ICE-First-Muscle Proteins (International Caenorhabditis elegans Experiment First Flight-Muscle Proteins),
Identifikatsia (Identification of the Sources of Dynamic Loads on ISS),
Inflight Education Downlinks (International Space Station Inflight Education Downlinks),
Interactions (Crewmember and Crew-Ground Interaction During International Space Station Missions),
Interleukin-K (Production of Hight Quality Crystals of Interleukin -1Alpha, -1Beta and Receptor of Antagonist of Interleukin-1),
Iskazheniye (Determination and Analysis of Magnetic Interference on ISS),
ISSI (In Space Soldering Investigation),
ISS Acoustics (International Space Station Acoustic Measurement Program),
Izgib (Effect of Performance of Flight and Science Activities on the Function of On-Orbit Systems on ISS (Mathematical Model)),
JAXA-GCF (Japan Aerospace and Exploration Agency - Granada Crystallization Facility High Quality Protein Crystallization Project),
Journals (Behavioral Issues Associated with isolation and Confinement: Review and Analysis of Astronaut Journals),
Kromka (Verification of the Effectiveness of Devices for the Protection of the Exterior Surface of ISS from Contaminants Deposited by Pulsed Cycling of Liquid-Jet),
Meteoroid (Recording Meteoroidal and Technogenic Particles on the External Surface of the Service Module of the Russian Segment of ISS),
Mezhkletochnoe Vzaimodeistvie (Intercellular Interactions in Space Flight),
MFMG (Miscible Fluids in Microgravity),
Mimetik-K (Crystalization of antigen Binding Fragment of Monoclonalical Antibody to Glucosaminilmuramildepeptide),
MISSE-1 and 2 (Materials International Space Station Experiment - 1 and 2),
Mobility (Promoting Sensorimotor Response Generalizability: A Countermeasure to Mitigate Locomotor Dysfunction After Long-Duration Space Flight),
Molniya-SM (Investigation of Lightning Discharges in the Earth's Atmosphere and Lower Ionosphere),
MOP (Motion Perception: Vestibular Adaptation to G-Transitions),
Muscle (Study of Low Back Pain in Crewmembers During Space Flight),
PCG-STES-RGE (Protein Crystal Growth-Single Locker Thermal Enclosure System-Regulation of Gene Expression),
PCG-STES-SA (Protein Crystal Growth-Single Locker Thermal Enclosure System-Science and Applications of Facility Hardware for Protein Crystal Growth),
Pilot (Individual Characteristics of Psychophysiological Regulatory Status and Reliaility of Professional Activities of Cosmonauts in Long Duration Space Flight),
Plasma_Crystal (Dusty and Liquid Plasma Crystals in Conditions of Microgravity),
Platan (Search for Low Energy Heavy Particles of Solar and Galactic Origin),
Plazmida (Transfer of Molecules of DNA by Conjugation in Space Flight),
Privyazka (Development of High Precision Orientation of Scientific Devices in Space with Reports of Deformation of the ISS Hull),
Profilaktika (Mechanisms of Action and Influence, and Effectiveness of Various Methods of Phrophylaxis Directed Toward Prevention of Disturbances of the Human Locomotion System in Weightlessness),
Prognoz (Development of a Method of Operational Prediction of Work Load on Crew Piloting Objectives),
Pulse (Vegatative (Autonomic) Regulation of the Cardio-Respiratory System of Humans in Conditions of Weightlessness),
Rastenia (Growth and Development of Higher Plants through Multiple Generations),
Relaksatia (Processes of Relaxation in the Ultraviolet Band Spectrum by High Velocity Interaction of Exhaust Products on ISS),
Sample (Study of Microbial Communities Exposed to Weightlessness),
Seeds (Seeds in Space),
SKR (Skorpion: Development and Acquisition of Multifunctional Control-Measurement Device for Controlling the Environment of Scientific Experiments Inside a Pressurized Station),
SNFM (Serial Network Flow Monitor),
Sprut-MBI (Determination of Intracellular and Extracellular Fluid Volume in Humans in Space Flight),
Tenzor (Definition of Dynamic Characteristics of ISS),
Toksichnost (Development of a Metod of Express Monitoring of Toxicity of Water in Space Flight),
Uragan (Hurricane: Experimental Development of Groundbased System of Monitoring and Predicting the Progression of a Naturally Occurring Technogenic Catastrophe),
Vaktsina-K (Structural Study of Protein Candidats in a Vaccine for AIDS on Earth and in Space),
Vektor-T (Study of a High Precision System for Prediction Motion of ISS).

André Kuipers am 30. April 2004 um 00:12 UTC mit Sojus TMA-3 gelandet.