Background : Warts are the common skin diseases. Warts are caused by infection with human papillomaviruses. Up to now, there is no standard treatment for warts available. Imiquimod 5% cream is currently approved as the treatment for external genital/perianal warts. It is an interesting alternative option to treat other types of warts. Objectives : We compared the safety, effectiveness and recurrent rate between topical 5% imiquimod and placebo under occlusion combined with 20% salicylic acid in the treatment of common warts. Methods : Thirty patients with common warts were recruited into this study. In each patient, at least two identical lesions at the symmetrical location on the opposite side of the body were selected for treatment. The patients were instructed to apply 20% salicylic acid ointment to each warts in the morning. At night, each identical wart was randomized to apply either 5% imiquimod cream or placebo cream under occlusion. The treatment was done only five days a week for 12 weeks or until the warts were completely disappeared. Follow up was done every 2 weeks to assess the effectiveness and side effects of the medications. For those whose warts were completely disappeared, 24 weeks follow up was done to evaluate the recurrent rate. Results : There were significant differences in effectiveness between the two groups (p = 0.002) and in volume reduction of common warts between the two groups (p < 0.001). Sixteen of 30 patients (53.3%) with warts achieved a total clearance after a mean treatment period of 8.625 weeks. No severe side effects were detected. The recurrent rate for patients using 5% imiquimod cream was 6.25%. Conclusion : 5% imiquimod cream under occlusion combines with 20% salicylic acid is an effective and safe self-administered therapy for common warts. The recurrent rate is low.