Stewart Cole achieved international recognition for his leadership of the project to sequence the genome of the bacterium responsible for tuberculosis, successfully completed in 1998. It was the first major pathogen to be sequenced, and the resulting data continues to furnish abundant opportunities to develop a new generation of treatments.

Stewart also participated in sequencing the genome of the AIDS virus, HIV type 1, and several human papilloma viruses. Genome biology underpins his efforts to develop new drugs for mycobacterial diseases: one class of agents, benzothiazinones, targets an enzyme essential to the formation of cell walls in Mycobacterium tuberculosis and is effective against both drug-sensitive and drug-resistant tuberculosis.

Stewart leads international collaborations into diseases including AIDS, tuberculosis and leprosy, which threaten public health in the developing world. In 2002, he gave the Marjory Stephenson Prize Lecture at the 150th anniversary meeting of the Society for General Microbiology. He was awarded the 2009 Kochon Prize and the 2014 Behring Prize, and has been elected to the French National Academy of Pharmacy and EMBO.