Euthanasia planners quickly envisioned extending the killing program to adult disabled patients living in institutional settings. In the autumn of 1939, Hitler signed a secret authorization in order to protect participating physicians, medical staff, and administrators from prosecution; this authorization was backdated to September 1, 1939, to suggest that the effort was related to wartime measures. The secret operation was code-named T4, in reference to the street address (Tiergartenstrasse 4) of the program's coordinating office in Berlin. Six gassing installations for adults were eventually established as part of the Euthanasia Program: Bernburg, Brandenburg, Grafeneck, Hadamar, Hartheim, and Sonnenstein.

Beginning in January 1940, adult patients were selected by specially recruited T4 physicians for death. These doctors rarely examined the patients themselves, but often based their decisions on medical files and the diagnoses of staff at the victims' home institutions. Those selected were transported by T4 personnel to the sanatoria that served as central gassing installations. The victims were told they would undergo a physical evaluation and take a disinfecting shower. Instead, they were killed in gas chambers using pure carbon monoxide gas. Their bodies were immediately burned in crematoria attached to the gassing facilities. Ashes of cremated victims were taken from a common pile and placed in urns without regard for accurate labeling. One urn was sent to each victim's family, along with a death certificate listing a fictive cause and date of death. The sudden death of thousands of institutionalized patients, whose death certificates listed strangely similar causes and places of death, raised suspicions. Eventually, the clandestine Euthanasia Program became an open secret.