BACKGROUND AND OBJECTIVES: Children with atopic dermatitis (AD) have a higher risk for development of food allergies. The objective of this study was to examine incidence of food allergy development in infants with AD and the predictive value of food-antigen-specific immunoglobulin E measurements. METHODS: This trial examined the long-term safety and efficacy of pimecrolimus cream 1% in >1000 infants (3-18 months) with mild-to-severe AD without a history of food allergy. Food allergy development was followed throughout a 36-month randomized double-blind phase followed by an open-label (OL) phase up to 33 months. Additionally, sIgE for cow's milk, egg white, peanut, wheat, seafood mix, and soybean was measured by ImmunoCAP at baseline, end of the double-blind phase, and end of OL phase. RESULTS: By the end of the OL phase, 15.9% of infants with AD developed at least 1 food allergy; allergy to peanut was most common (6.6%), followed by cow's milk (4.3%) and egg white (3.9%). Seafood, soybean, and wheat allergies were rare. Levels of sIgE for milk, egg, and peanut increased with severity of AD, as determined by Investigator's Global Assessment score. We assigned sIgE decision points for the 6 foods and tested their ability to predict definite food allergy in this population. Positive predictive values for published and newly developed sIgE decision points were low (<0.6 for all values tested). CONCLUSIONS: In a large cohort of infants at risk for development of food allergy, sIgE levels were not clinically useful for predicting food allergy development.