Iron plus folate supplementation increases mortality and morbidity among children in areas of malaria endemicity in Africa, but the effects of supplementation on pregnant women in malaria-endemic areas remain unclear. In northeastern Tanzania, where malaria and iron deficiency are common, we found that placental malaria was less prevalent (8.5% vs. 47.3% of women; P< .0001) and less severe (median parasite density, 4.2% vs. 6.3% of placental red blood cells; P< .04) among women with iron deficiency than among women with sufficient iron stores, especially during the first pregnancy. Multivariate analysis revealed that iron deficiency (P< .0001) and multigravidity (P< .002) significantly decreased the risk of placental malaria. Interventional trials of iron and folate supplementation during pregnancy in malaria-endemic regions in Africa are urgently needed to ascertain the benefits and risks of this intervention.