DeBakey continued to practice medicine until his death in 2008 at the age of 99. His contributions to the field of medicine spanned the better part of 75 years. DeBakey operated on more than 60,000 patients, including several heads of state. DeBakey and a team of American cardiothoracic surgeons, including George Noon, supervised quintuple-bypass surgery performed by Russian surgeons on Russian president Boris Yeltsin in 1996.
On July 11, 2008, DeBakey died at Houston Methodist in Houston, two months before his 100th birthday; the cause of death remained unspecified. After lying in repose in Houston's City Hall, the first ever to do so, DeBakey received a memorial service at the Co-Cathedral of the Sacred Heart on July 16, 2008. He was granted ground burial at Arlington National Cemetery by the Secretary of the Army. On January 21, 2009, DeBakey became the first posthumous recipient of the Denton A. Cooley Leadership Award.
The Albert Lasker Award for Clinical Medical Research, given by the Lasker Foundation since 1946, was renamed the Lasker-DeBakey Clinical Medical Research Award in DeBakey's honor in 2008.
In early 2008, DeBakey attended the groundbreaking for the new Michael E. DeBakey Library and Museum at Baylor College of Medicine in Houston, which honors his life, work and dedication to care and teaching. The museum officially opened on Friday, May 14, 2010.