In 1983, Thacker was a founder of the Systems Research Center (SRC) of Digital Equipment Corporation (DEC), and in 1997, he joined Microsoft Research to help establish Microsoft Research Cambridge in Cambridge, England.
After returning to the United States, Thacker designed the hardware for Microsoft's Tablet PC, based on his experience with the "interim Dynabook" at PARC, and later the Lectrice, a pen-based hand-held computer at DEC SRC.