Background: Pyogenic granuloma is a benign vascular proliferation that is often related to minor trauma by the patient. Objective: Evaluation of the efficacy of cryotherapy in the treatment of pyogenic granuloma. Patients and Methods: Hundred and forty-six patients with pyogenic granuloma were treated by cryosurgery using liquid nitrogen and cotton tip applicator in an open clinical trial. This study was carried out in Razi Hospital, Tehran University of Medical Sciences, in 1377. Patients were followed for at least 3 months after complete resolution. Results: Hundred and thirty-five patients completed the study. Complete resolution was achieved in all patients. Treatment sessions ranged from one to 4 (Mean 1.6±0.8) sessions. 88.2% of patients needed only 1 or 2 treatment sessions. Recurrence of lesions occurred in 3 patients in whom retreatment led to complete resolution. Conclusion: Cryotherapy can be regarded as a completely efficient method in treatment of pyogenic granuloma.