OBJECTIVE To investigate the risk factors for cotton-wool spots and for cytomegalovirus retinitis in patients with human immunodeficiency virus infection (HIV). METHODS A cross-sectional study was performed on 453 consecutive male patients with a positive serodiagnosis for HIV. The possible risk factors of age, race, absolute T-lymphocyte CD4+ count, and mode of HIV acquisition were evaluated. RESULTS Age and race were not significant predictors of either cotton-wool spots or cytomegalovirus retinitis. Low CD4+ T-lymphocyte counts were the strongest predictor of both types of retinopathy. After adjustment for CD4+ T-lymphocyte counts by logistic regression, patients who had acquired HIV through homosexual or bisexual activity were more likely to have cotton-wool spots (odds ratio, 2.09; P = 0.029) and cytomegalovirus retinitis (odds ratio, 4.14; P = 0.0028) than were patients who had acquired the disease intravenously. CONCLUSIONS The results of this study showed that the ocular manifestations of HIV infection are associated with low CD4+ counts and HIV acquisition through bisexual or homosexual activity. Patients with these risks factors should be targeted for prophylaxis and prevention strategies for cytomegalovirus retinitis.