We examined the association of placental malaria and mother-to-child transmission (MTCT) of HIV in a prospective community-randomized trial in Rakai District, Uganda. In the 746 HIV-positive mother-infant pairs, the MTCT rate was 20.4%. Placental malaria was more common in HIV-positive than HIV-negative women. After multivariate adjustment for HIV viral load, the risk of MTCT associated with placental malaria was 2.89 and with HIV viral load the risk was 2.85. Interventions to prevent malaria during pregnancy could potentially reduce MTCT.