The safety and effectiveness of imiquimod cream 5% were evaluated in the treatment of molluscum contagiosum (MC) in children. Twenty-three children ranging in age from 1 to 9 years with MC infection were randomized to either imiquimod cream 5% (12 patients) or vehicle (11 patients). Parents applied study drug to patient's lesions 3 times a week for 12 weeks. Patients presented to the clinic every 2 weeks until the end of study (week 12) for safety evaluation and lesion count. Local skin reactions, partial and complete clearances, and lesion counts were statistically analyzed. Partial clearance (≥30% clearance of lesions) at weeks 4 and 12 was noted in 58.3% (7/12) and 66.7% (8/12) of imiquimod patients and in 0% (0/11) and 18.2% (2/11) of vehicle patients (imiquimod vs vehicle: week 4, P = .0046; week 12, P = .0361). Complete clearance at week 12 was noted in 33.3% (4/12) of imiquimod patients and in 9.1% (1/11) of vehicle patients. The mean percentage change in lesion count at week 12 was -45.9% in the imiquimod group and +26.9% in the vehicle group. Imiquimod was well tolerated and appears to be a promising therapeutic option in the treatment of MC in children. Larger studies are needed to confirm the results of this small pilot study.