OBJECTIVES: To determine the association between maternal multivitamin supplementation and the mental and psychomotor development of children who are born to HIV-1-infected mothers in Tanzania, as secondary endpoints in a randomized trial that investigated the effect of maternal multivitamin supplementation on HIV-1 vertical transmission and progression. METHODS: The Bayley Scales of Infant Development, 2nd Edition, were administered at 6, 12, and 18 months of age to a subset of children (N = 327). We assessed the effect of vitamin A and multivitamin (vitamins B, C, and E) supplementation using linear regression models and Cox proportional hazard models for the Mental Development Index, the Psychomotor Development Index, and raw scores separately. RESULTS: Multivitamin supplementation was associated significantly with a mean increase in Psychomotor Development Index score of 2.6 (95% confidence interval: 0.1-5.1). Multivitamins were also significantly protective against the risk for developmental delay on the motor scale (relative risk: 0.4; 95% confidence interval: 0.2-0.7) but not on the Mental Development Index. Vitamin A supplementation had no significant effect on these outcomes. CONCLUSIONS: Maternal multivitamin supplements provide a low-cost intervention to reduce the risk for developmental delays among infants who are born to HIV-positive mothers in developing countries.