We reviewed records of 378 patients who died after cardiac valve replacement and underwent autopsy at The Methodist Hospital, Houston, from 1962 through 1979. Patients were divided according to postoperative interval at death: within 30 days (early) or 30 days to ten years (late). Early deaths (279 patients) were due almost exclusively to cardiovascular abnormalities or operative complications (94%). Only 6% of early deaths were caused by prosthesis-associated complications. In contrast, late deaths (99 patients) were valve related in 47% of cases, including complete thrombotic occlusion or systemic thromboembolism (21%), prosthetic valve endocarditis (14%), valve dehiscence (6%), anticoagulation-related hemorrhage (3%), and mechanical degeneration (2%). Nine percent of late deaths were unrelated to cardiovascular disease. Thus, while early deaths primarily reflected the severity of preexisting or associated cardiovascular disease, prosthesis-associated complications were an important cause of late death after cardiac valve replacement.