Clinical manifestations, course, and outcome of Mycobacterium avium complex (MAC) infection have not been well described. We performed a retrospective review of MAC infection in both HIV-infected and non-HIV–infected population at a large urban community hospital. Medical records of patients at Albert Einstein Medical Center, Philadelphia, in whom bacteriologic specimens grew MAC who met criteria for infection, between December 2006 and January 2011 were reviewed. A total of 38 patients, of whom 19 were HIV infected, were reviewed. Among the HIV-infected group, 15 had disseminated infection. Mean CD4 counts was 20 cells/mm3 (±19 SD). The most common presentation was retroperitoneal lymphadenopathy. Pericardial effusion was found in 20% (n=3). Fourteen patients (93%) received therapy. Nine (60%) died and median time to death was 11 months (range, 3 to 21 mo). Four patients with HIV infection had isolated pulmonary MAC infection with mean CD4 counts of 275 cells/mm3 (±386 SD). Three had structural lung disease. Of the 19 patients without HIV infection, 13 had underlying lung disease, 3 were taking immunosuppressive medications, and 3 were apparently healthy. Among the 8 patients with underlying lung disease who received therapy, 4 achieved sputum conversion, whereas 3 had bacteriologic failure. The latter remained stable despite treatment discontinuation. Isolated pulmonary MAC infection occurred at higher CD4 counts in HIV-infected patients who had structural lung disease. A significant proportion of patients with disseminated MAC were found to have pericardial effusion. Absence of disease progression was noted in HIV-uninfected patients despite bacteriologic failure.