Pyruvate dehydrogenase is an enzyme that catalyzes the reaction of pyruvate and a lipoamide to give the acetylated dihydrolipoamide and carbon dioxide. The conversion requires the coenzyme thiamine pyrophosphate.

Pyruvate dehydrogenase is usually encountered as a component, referred to as E1, of the pyruvate dehydrogenase complex (PDC). PDC consists of other enzymes, referred to as E2 and E3. Collectively E1-E3 transform pyruvate, NAD⁺, coenzyme A into acetyl-CoA, CO₂, and NADH. The conversion is crucial because acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration. To distinguish between this enzyme and the PDC, it is systematically called pyruvate dehydrogenase (acetyl-transferring).