BACKGROUND: Cutaneous leishmaniasis (CL) is a serious public health problem in many tropical and subtropical regions of the world. Treatment of CL can prevent disfiguring scars. AIM: The efficacy of local heat therapy by radiofrequency (RF) was compared with intralesional injection of meglumine antimoniate in the treatment of CL. METHODS: This was a randomized clinical trial. Patients with antroponotic cutaneous leishmaniasis (ACL) in the Isfahan province of Iran were enrolled in the study if the examination of a smear from a suspected CL lesion was confirmed positive for Leishmania. Patients were randomly allocated to one of two treatment groups. Group A was treated by heat therapy by RF at 50 degrees C for 30 s once weekly for 4 weeks, and group B was treated with intralesional injection of meglumine antimoniate once weekly for 4 weeks. Follow-up lasted 6 months. Response to treatment was classified as complete (lesions flattened, no induration, and epidermal creases had appeared), partial (reduction in lesion size, but without the appearance of epidermal creases) and poor (no reduction in lesion size). RESULTS: Of 117 participants, 57 patients with 83 lesions in group A and 60 patients with 94 lesions in group B completed the study and were followed up for 6 months. Complete, partial and poor response to treatment were 80.7%, 12% and 7.3% in group A, and 55.3%, 21.27% and 23.40% in group B, respectively (P = 0.001). In both groups, there was no relapse in patients with complete response after 6 months of follow-up. CONCLUSIONS: Heat therapy with thermogenerator RF can be used as an efficacious treatment in the lesions of CL. It is more effective than the conventional treatment with intralesional meglumine antimoniate injection.