To compare the efficacy, safety and acceptability of imiquimod (IMQ) 5% cream with cryotherapy for the treatment of molluscum contagiosum (MC) in children. Prospective, randomized, comparative, observer blinded study. A total of 74 children, with MC were divided randomly to receive treatment with either IMQ 5% cream (group A) 5 days a week or cryotherapy (group B) once a week until clinical cure or up to a maximum of 16 weeks. All the patients were followed up weekly during active treatment. The patients were followed-up for 6 months after clinical cure to look for recurrence. In the IMQ group (group A), the overall complete cure rate was 91.8% (34 of 37), 22 of the 37 patients cleared by the end of 6 weeks and 12 more patients cleared by the end of 12 weeks, while the remaining three patients (8.1%) did not clear even after 16 weeks. Whereas, in the cryotherapy group, all 37 patients achieved complete cure, 26 of 37 (70.27%) patients cleared after 3 weeks, and the remaining 11 (29.72%) cleared by the end of 6 weeks. No statistically significant difference was found between the overall complete cure rate in both groups at the end of maximum treatment period (16 weeks). Pain, bullae formation, pigmentary changes, and superficial scarring were more significantly common in the cryotherapy group compared with the IMQ group. Imiqimod 5% cream seems to be slow acting but an effective agent for the treatment of MC in children. IMQ appears to be practically painless and more cosmetically accepted treatment when compared with cryotherapy, and may be the preferred treatment of MC in children especially with numerous small lesions. Cryotherapy has the advantage of being rapidly effective, and is less expensive than IMQ and may be the preferred treatment for large solitary or few lesions.