BACKGROUND AND OBJECTIVES: Most osteopaths are trained in pediatric care, and osteopathic manipulative treatment (OMT) is available for many pediatric conditions. The objective of this systematic review was to critically evaluate the effectiveness of OMT as a treatment of pediatric conditions. METHODS: Eleven databases were searched from their respective inceptions to November 2012. Only randomized clinical trials (RCTs) were included, if they tested OMT against any type of control in pediatric patients. Study quality was critically appraised by using the Cochrane criteria. RESULTS: Seventeen trials met the inclusion criteria. Five RCTs were of high methodological quality. Of those, 1 favored OMT, whereas 4 revealed no effect compared with various control interventions. Replications by independent researchers were available for 2 conditions only, and both failed to confirm the findings of the previous studies. Seven RCTs suggested that OMT leads to a significantly greater reduction in the symptoms of asthma, congenital nasolacrimal duct obstruction (posttreatment), daily weight gain and length of hospital stay, dysfunctional voiding, infantile colic, otitis media, or postural asymmetry compared with various control interventions. Seven RCTs indicated that OMT had no effect on the symptoms of asthma, cerebral palsy, idiopathic scoliosis, obstructive apnea, otitis media, or temporomandibular disorders compared with various control interventions. Three RCTs did not perform between-group comparisons. The majority of the included RCTs did not report the incidence rates of adverse effects. CONCLUSIONS: The evidence of the effectiveness of OMT for pediatric conditions remains unproven due to the paucity and low methodological quality of the primary studies.