Background: An easy and effective topical treatment is not yet available for cutaneous leishmaniasis. Objectives: To compare the effect of topical trichloroacetic acid (TCA) and intralesional glucantime injection in the treatment of acute wet cutaneous leishmaniasis. Patients and Methods: Eighty patients with clinical diagnosis of wet cutaneous leishmaniasis in the age range of 5 to 75 years were recruited in this open clinical trial. Seven patients were withdrawn during the trial. In TCA group, 38 patients were treated three times (Every 2 weeks) with 50% TCA. In control group, 35 patients received intralesional glucantime injection weekly until healing or for a maximum of 6 weeks. All patients were followed for 3 months after last treatment. Results: After four weeks of treatment, 20 patients (52.6%) in TCA group and 17 patients (48.5%) in glucantime group, and after six weeks, 68% and 65.7% of patients in each respective group were completely cured. There was no important side effect in any groups. Conclusion: The nearly equal efficacy of TCA peeling and intralesional glucantime injection in the treatment of cutaneous leishmaniasis suggests that 50% TCA could be considered as a possible efficient therapeutic alternative in the management of this disease.