Background: Common wart is one of the most prevalent skin diseases, caused by human papilloma virus. Numerous therapeutic modalities have been used in the treatment of warts. Objectives: This study was designed to evaluate and compare the efficacy of 5% 5-fluorouracil (5-FU) ointment with cryotherapy in the treatment of common warts of hands. Patients and Methods: In a single blind, prospective clinical trial, 30 patients with bilateral common warts of hands referred to Dermatology Clinic of Razi Hospital, were recruited. The lesions on one hand of the patients were treated by cryosurgery and on the other hand with 5% 5-FU ointment twice daily for about 12 weeks. Results: After 12 weeks, 93% of patients treated by cryotherapy (The mean treatment period 7.5 weeks), and 66.7% of patients received 5% 5-FU ointment (The mean treatment period 6.9 weeks) were completely cured. No significant side effects were noted in patients who received 5% 5-FU ointment. Conclusion: 5% 5-FU ointment can be used as appropriate, household and inexpensive treatment in the management of common warts.