Although reports suggest that infant mortality is increased during iodine deficiency, the effect of iodine supplementation on infant mortality is unknown. A double-masked, randomized, placebo-controlled, clinical trial of oral iodized oil was conducted in Subang, West Java, Indonesia to evaluate the effect of iodine supplementation on infant mortality. Infants were allocated to receive placebo or oral iodized oil (100 mg) at about 6 wk of age and were followed to 6 mo of age. Six hundred seventeen infants were enrolled in the study. Infant survival was apparently improved, as indicated by a 72% reduction in the risk of death during the first 2 mo of follow-up (P < 0.05) and a delay in the mean time to death among infants who died in the iodized oil group compared with infants who died in the placebo group (48 days vs. 17.5 d, P = 0.06). Other infant characteristics associated with reduced risk of death included weight-for-age at base line, consumption of solid foods, female gender and recent history of maternal iodine supplementation. Oral iodized oil supplementation had a stronger effect on the mortality of males compared with females. This study suggests that oral iodized oil supplementation of infants may reduce infant mortality in populations at risk for iodine deficiency.