Objective: To test whether zinc supplementation during pregnancy would reduce infant morbidity rates. Study design: A double-blind, randomized controlled trial of prenatal zinc supplementation was conducted from 1995 to 1997 in a periurban slum of Lima, Peru. Participants were randomly assigned to receive daily supplementation with zinc (15 mg zinc + 60 mg iron + 250 μg folic acid) or placebo (60 iron + 250 μg folic acid) from 10 to 24 weeks gestation until 1 month postpartum. Anthropometry was measured monthly from birth through age 12 months, and morbidity and dietary intake were measured weekly from 6 to 12 months (n = 421). Results: The average percentage of observation days with diarrhea among infants prenatally treated with zinc (5.8%) was reduced compared with infants in the control group (7.7%) (P = .01). Prenatal zinc supplementation reduced the likelihood of an infant experiencing diarrheal episodes of acute diarrhea lasting longer than 7 days (OR 0.66, 95% CI 0.43, 0.99, P = .04) and mucus in the stool (OR 0.65 95% CI 0.46, 0.92, P = .01) adjusting for infant age, breastfeeding, season, and hygiene and sanitation covariates. No treatment effects on respiratory illnesses, fever, or skin conditions were detected. Conclusions: Improving prenatal zinc nutrition protected against diarrheal morbidity in infant offspring through 12 months of age. © 2010 Mosby, Inc. All rights reserved.