OBJECTIVE: The aim of the present study was to evaluate the efficacy of a milkfat globule membrane (MFGM)-enriched protein fraction in a complementary food, on diarrhea, anemia, and micronutrient status. SUBJECTS AND METHODS: A randomized, double-blind controlled design to study 550 infants, 6 to 11 months old, who received daily for 6 months a complementary food (40g/day) with the protein source being either the MFGM protein fraction or skim milk proteins (control). Health and nutritional status of infants were examined monthly in the outpatient clinic; product intake, food patterns, and diarrhea morbidity were assessed by home visits twice per week. Hemoglobin and micronutrient status were measured at 0 and 6 months of intervention. Results are presented as the entire group and as 6 to 8 and 9 to 11 months subgroups. RESULTS: A total of 499 infants completed the study. Global prevalence of diarrhea was 3.84% and 4.37% in the MFGM group and control group, respectively (P<0.05). Consumption of the MFGM protein fraction reduced episodes of bloody diarrhea (odds ratio 0.54; 95% confidence interval 0.31-0.93, P=0.025) adjusting for anemia and potable water facilities as covariates. There were no differences between groups in anemia, serum ferritin, zinc, or folate. CONCLUSIONS: Addition of an MFGM-enriched protein fraction to complementary food had beneficial effects on diarrhea in infants and may thus help to improve the health of vulnerable populations. Copyright © 2011 by ESPGHAN and NASPGHAN.