Background: There is evidence to support the use of lipid-based nutrient supplements (LNSs) to promote child growth and development in low-income countries, but there is also a concern regarding the safety of using iron-fortified products in malaria-endemic areas. Objective: The objective of this study was to test the hypothesis that 6-to 18-mo-old rural Malawian children receiving iron-containing (6 mg/d) LNSs would not have excess morbidity compared with infants receiving no supplementation. Methods: A randomized controlled trial allocated 840 children to receive daily supplementation with 54 g/d LNS with milk protein base (milk-LNS), 54 g/d LNS with soy protein base (soy-LNS), 71 g/d corn-soy blend (CSB), or no supplementation from 6 to 18mo of age.Morbiditywas compared using a non-inferioritymargin set at 20%excess morbidity in supplemented groups compared with the nonsupplemented group. Results: Baseline characteristics were similar across groups. The proportion of days with febrile illness between 6 and 18 mo was 4.9%, and there were no differences between the groups: 4.9% (95% CI: 4.3, 5.5%), 4.5% (95% CI: 3.9, 5.1%), 4.7% (95% CI: 4.1, 5.3%), and 5.5% (95% CI: 4.7-6.3%) in the milk-LNS, soy-LNS, CSB, and control groups, respectively. The proportion of days with respiratory problems and diarrhea between 6 and 18 mo also did not differ between groups. Compared with controls, the incident rate ratio (95% CI) for clinical malaria was 0.80 (0.59, 1.09), 0.77 (0.56, 1.06), and 0.79 (0.58, 1.08) in milk-LNS, soy-LNS, and CSB, respectively, with 95% CIs confirming non-inferiority. The incidence of febrile episodes, diarrhea, respiratory problems or admission to hospital, prevalence of malaria parasitemia throughout the follow-up, and mean change in hemoglobin concentration from baseline were also similar between the groups. Conclusions: Daily supplementation with 54 g of milk-based or soy protein-based LNS or 71 g of CSB did not result in increases in malaria or respiratory morbidity in children in a malaria-endemic setting. However, we could not conclude whether LNSs did or did not increase diarrheal morbidity.