Background: Cutaneous leishmaniasis (CL) is a parasitic disease caused by leishmania species. An ideal treatment for CL has not found yet. Objectives: To evaluate the efficacy of cryotherapy alone and combined with intralesional glucantime injection in the treatment of papulonodular CL. Patients and Methods: 300 patients with CL were randomly assigned to two treatment groups in this clinical trial. In group 1, 100 patients with 149 lesions were treated with cryotherapy plus intralesional glucantime injection every 2 weeks. In group 2, 200 patients with 230 lesions were treated only with cryotherapy, every 2 weeks. Both groups were followed for 6 months after last treatment. Results: Clinical and parasitological cure were seen in 90% of cases in group 1 and 57.3% in group 2 (P<0.05). Conclusion: Combination of cryotherapy and intralesional glucantime injection is an effective treatment modality in early lesions of CL.