A nested case-control study of vitamin A deficiency and wasting as risk factors for mortality from AIDS and infections was done within a large prospective cohort of human immunodeficiency virus (HIV)-infected injection drug users (IDUs). Fifty adult subjects who died from AIDS and infections were matched with 235 controls who survived. Plasma vitamin A, weight, and body mass index were measured. Mean length of follow-up was 2.4 +/- 1.1 years. Vitamin A deficiency occurred in 50% and wasting occurred in 38% of patients in the last visit before death. CD4 cells count < 200/microL, wasting, and vitamin A deficiency were associated with mortality. There was a higher risk of death in HIV-infected subjects with vitamin A deficiency (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.8-11.3) and wasting (OR, 8.8; 95% CI, 2.7-28.2). Vitamin A deficiency and wasting are common during HIV infection and are independent predictors of mortality in HIV-infected IDUs.