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To evaluate whether clinical data support the safety and efficacy of probiotics for the management of infantile colic.Probiotics have been suggested as a potential strategy for infantile colic, and the specific species that have been studied in healthy infants are considered to be safe.A systematic review was conducted to identify randomized controlled trials (RCTs) evaluating the use of probiotic supplementation in infants with colic. RCTs with a primary end point assessing crying or fussing time were selected. A meta-analysis comparing “responders” to “nonresponders” in infants receiving probiotic versus control was conducted. The quality of trials selected was assessed.Five RCTs assessing 2 different strains of the probiotic Lactobacillus reuteri in mostly breastfed infants were identified. Analysis of response rates showed that infants receiving probiotics had a 2.3-fold greater chance of having a 50% or greater decrease in crying/fussing time compared to controls (P = .01). Probiotic supplementation was not associated with any adverse events.Supplementation with the probiotic L. reuteri in breastfed infants appears to be safe and effective for the management of infantile colic. Further research is needed to determine the role of probiotics in infants who are formula-fed.