Background: Cutaneous leishmaniasis is an endemic disease in Iran. Pentavalent antimonial drugs have been the first line of therapy in cutaneous leishmaniasis for many years. However, the cure rate of these agents is still not favorable. This study was carried out to compare the effects of topical trichloroacetic acid 50% in combination with glucantime, intralesional glucantime plus fractional laser, and glucantime alone on cutaneous leishmaniasis. Methods: A total of 90 patients were randomly divided into three groups of 30 to be treated with intralesional injection of meglumine antimoniate (glucantime), a combination of topical trichloroacetic acid 50% and glucantime, or a combination of fractional laser and glucantime. Complete cure rate and changes in sizes of lesions and scars were assessed and compared between groups. Findings: The mean duration of treatment was 6.1 ± 2.1 weeks in all patients (range: 2-12 weeks) and 6.8 ± 1.7, 5.2 ± 1.0, and 6.3 ± 3.0 weeks in glucantime, topical trichloroacetic acid plus glucantime, and fractional laser plus glucantime groups, respectively (P = 0.011). The mean score of scars was 3.7 ± 0.6, 3.6 ± 0.8, and 6.3 ± 0.7 in the above-mentioned groups (P < 0.001). Conclusion: Compared to glucantime alone, the combination of intralesional glucantime and trichloroacetic acid 50% or fractional laser had significantly higher and faster cure rate in patients with cutaneous leishmaniasis. Keywords: Meglumine antimoniate, Glucantime, Trichloroacetic acid, Fractional laser, Cutaneous leishmaniasis