On 5 August 2009, Dutch minister of economic affairs Maria van der Hoeven, announced Kuipers was selected as an astronaut for International Space Station (ISS) Expeditions 30 and 31.

In May 2009, he served as the backup of Belgian astronaut Frank de Winne, who later became the Expedition 21 commander, during the later part of his six-month mission.

As part of his DELTA mission, Kuipers conducted 21 experiments[7] in orbit on a wide range of subjects: physiology, biology, microbiology, medicine, technological development, physics and Earth observation.

The so-called Arges project, of which Kuipers' experiment formed a part, was commissioned by Eindhoven University of Technology and Philips Electronics.

On 26 November 2008, Dutch minister of economic affairs Maria van der Hoeven pushed for a second, six-month mission for Kuipers in 2011.

Kuipers launched on 21 December 2011 on the Soyuz TMA-03M flight with his two fellow crew members Cosmonaut Oleg Kononenko from the Russian Space Agency Roscosmos, and Don Pettit from NASA.