Introduction: Cutaneous Leishmaniasis (CL) is an endemic parasitic disease in Iran. The residual unpleasant scar of this disease could be a potentially serious psychological threat to the patients. Based on the results of our previous study on the efficacy of trichloroacetic acid (TCA) in the treatment of CL, this study was designed to evaluate the effect of topical 5% TCA cream in the treatment of papulonodular leishmaniasis lesions Methods: In this case series study, among the patients who were referred to skin disease and leishmaniasis research center(SDLRC), 16 patients with positive direct smear for leishmaniasis were randomly selected for treatment with 5% TCA cream or, twice a day for 8 weeks or up to complete healing(epithelization)of the lesions. At the end of the treatment period, the response rate was assessed as complete cure, partial cure or treatment failure. The size of the scar was measured 6 months after complete epithelization of the lesions. The data were analyzed using SPSS version 12 Results: The mean area of the lesions was 38.81± 81.9 mm2 before the treatment, and 3.6±9.1 mm2 at 6 month follow up period. Complete cure was achieved in 1 patient (6.3%) at week 2, in 13 patients (86.7%) at week 7, and in all patients at week 8. There was no serious reaction in none of the patients. Only one patient had mild erythema at week 2 and edema at the application site at week 5 which completely was resolved within 2 weeks Conclusion: Our results showed complete cure in all cases at week 8 without any serious side effects. Considering the efficacy of TCA in decreasing the size of the residual scar and its low cost compared to other treatments, 5% TCA cream could be considered as an alternative modality for intralesional glucantime in the treatment of CL. Further assessment as a double blind randomized clinical trial is warranted