[5] Ratcliffe is best known for his work on cellular reactions to hypoxia, for which he shared the 2019 Nobel Prize in Physiology or Medicine with William Kaelin Jr. and Gregg L.

[14] In 1990, Ratcliffe received a Wellcome Trust Senior Fellowship to study cellular responses to hypoxia from low oxygen levels in the blood.

[17] In 1989, Ratcliffe established a laboratory in Oxford University's Nuffield Department of Medicine to explore the regulation of erythropoietin (EPO), a hormone released by the kidneys and responsible for stimulating the production of red blood cells.

From his studies, Ratcliffe discovered that the mRNA from kidneys that were part of the EPO production pathway that were capable of detecting hypoxia was also present in several other organs, both human and animal, including the spleen, brain, and testes.

[18] Building on these discoveries, the Ratcliffe group, along with joint studies with William Kaelin and Gregg Semenza, helped to uncover a detailed molecular chain of events that cells use to sense oxygen.

[13] The understanding of the molecular pathway of EPO production from hypoxia has led to the development of drugs that block VHL from binding with HIF to help treat patients with anaemia and kidney failure.