Miguel Ondetti earned his Ph.D. from the University of Buenos Aires. In 1960 he joined the Squibb Institute for Medical Research, where he spent his entire career. Ondetti and his colleague, David Cushman, employed rational design to produce the first ACE inhibitor, captopril.
Ondetti and Cushman shared the 1982 GlaxoSmithKline Alfred Burger Award in Medicinal Chemistry. They also shared the 1999 Albert Lasker Award for Clinical Medical Research and were named "Heroes of Chemistry" by the American Chemical Society. In 1991 Ondetti was awarded the Perkin Medal.