Thirsk was a member of the Expedition 21 crew on the International Space Station. He launched as a Flight Engineer on the Soyuz TMA-15 Soyuz mission on May 27, 2009, as a member of the Expedition 20 crew. He was the first Canadian astronaut to fly on a Soyuz. About this mission, Thirsk is quoted saying "It will be the supreme thrill of my life. Throughout the mission I will examine the long-term effects of zero gravity as both a test subject and a physician. My findings will undoubtedly contribute to the future understanding of space station living." He returned to Earth on Soyuz TMA-15 in November 2009.