There are few reports of the natural history of human immunodeficiency virus (HIV) infection from Asia. In a retrospective analysis of 594 patients (72.9% male; baseline CD4 cell count, 216 cells/microL) receiving care at YRG Center for AIDS Research and Education, a tertiary HIV referral center in southern India, the mean duration of survival from serodiagnosis was 92 months. Ninety-three percent of the patients acquired infection through heterosexual contact. The most common acquired immune deficiency syndrome-defining illnesses were pulmonary tuberculosis (49%; median duration of survival, 45 months), Pneumocystis carinii pneumonia (6%; median duration of survival, 24 months), cryptococcal meningitis (5%; median duration of survival, 22 months), and central nervous system toxoplasmosis (3%; median duration of survival, 28 months). Persons with a CD4 lymphocyte count of <200 cells/microL were 19 times (95% confidence interval [CI], 5.56-64.77) more likely to die than were those with CD4 cell count of >350 cells/microL. Patients who had > or =1 opportunistic infection were 2.6 times more likely to die (95% CI, 0.95-7.09) than were those who did not have an opportunistic infection. Antiretroviral therapy for patients with low CD4 lymphocyte counts improved the odds of survival (odds ratio, 5.37; 95% CI, 1.82-15.83).