Disseminated Mycobacterium avium complex disease remains a substantial cause of morbidity and mortality among patients with acquired immunodeficiency syndrome. From 1985 through 2000, we studied 1458 consecutive patients at Grady Memorial Hospital, Atlanta, with disseminated M. avium complex disease. There was a peak of 198 patients in the 1995, which decreased to 66 patients in 2000. In 1997, significantly more patients than in 1991 or 1994 were female (P<.001) or black (P<.001) and significantly fewer had acquired human immunodeficiency virus through homosexual contact (P<.001). In 1997, 50 (51%) of 99 of patients acquired M. avium complex disease despite receiving antimicrobial prophylaxis, but 32 (89%) of 36 patients did not adhere to the prophylaxis regimen. The median duration of survival of patients in 1991 was 110 days, whereas in 1994 it was 185 days, and in 1997 it was 339 days (P<.001). Prolonged survival was associated with receiving therapy that included clarithromycin and receiving combination antiretroviral therapy that included a protease inhibitor.