During the launch processing in March 2011, the Technical Management on Human Space System Flight Testing reported an operational glitch of the Kvant-V equipment.

Russian Space Agency Roscosmos established a working group with representatives from RSC-Energia and TSNIImash, the manufacturers and developers of the Soyuz systems.

[11] Roscosmos' Gagarin Cosmonaut Training Center (GCTC) hosted a two-day exam session for the prime and backup crews of Soyuz TMA-21 on March 4–5.

Souyz Commander Samokutyaev was launched from the Soyuz's center seat with flight engineer Borisenko strapped in to his left and NASA astronaut Ronald Garan on his right.

Hanging in front of the crew, live NASA TV launch footage showed that the dog begun to float as the spacecraft soared skywards, an indication of the weightlessness of space.

They were welcomed aboard for a crew greeting ceremony and a mandatory safety orientation by Expedition 27 Commander Dmitry Kondratyev and Flight Engineers Catherine Coleman and Paolo Nespoli.

Soyuz Commander Aleksandr Samokutyayev and Flight Engineers Andrei Borisenko and Ronald Garan returned to Earth on September 16, 2011 at 03:59 UTC, landing on target in central Kazakhstan.

[22] Russian search and rescue teams, along with NASA flight surgeons and space station program managers, were standing by to help the Soyuz crew.

After quick medical examinations inside a nearby erected tent, the crew were flown to Karaganda for an official welcome home ceremony.

From there Samokutyaev and Borisenko flew to Star City near Moscow while Garan boarded a NASA jet to fly back to the Johnson Space Center in Houston.