BACKGROUND: Cutaneous leishmaniasis is a common disease in Iran, especially in the north-east, central and southern parts of the country. Many treatments have been suggested for this disease but none is completely effective and without side-effects such as pain, arthralgia and renal or cardiac complications. Lasers have been used for treatment of several skin diseases since 1970, and CO(2) lasers are now being used for treatment of leishmaniasis. In this study, a CO(2) laser (Sonic 500 machine) was used as a source of a continuous CO(2) laser wave. METHODS: A total of 123 patients (68 female and 55 male) with 183 lesions were treated with the CO(2) laser. The maximum power was 100 W and the pulse width was 0.5-5 s. For the control group, 110 patients (with 250 lesions) were treated with glucantime 50 mg/kg/day for 15 days and, after 15 days of rest, this treatment was repeated (Glucantime Amps, 1.5 g in a 50-mL solution, was used). For follow-up, the patients were visited 1, 3, 4, 8, 12 and 24 weeks after treatment and any complications, recurrences or other wound characteristics were recorded. In the second group, Finally, all collected data were analyzed statistically. RESULTS: Statistical analysis with the chi(2) test showed that treatment with the CO(2) laser was more effective than treatment with glucantime (P = 0.0007). Complications were also seen less often with the laser treatment than with glucantime and were limited to the ulcer site. The CO(2) laser was more effective in treating cutaneous leishmaniasis than glucantime (1.12 times), had fewer side-effects (4.5% vs. 24%) and resulted in a shorter healing time (1 month vs. 3 months), and treatment could be applied in a single session. CONCLUSIONS: The results of this and previous studies suggest that cutaneous leishmaniasis can be treated effectively with CO(2) laser if those providing the treatment are sufficiently experienced. Laser treatment is more cost-effective than other treatments and can be used as first-line therapy for cutaneous leishmaniasis (wet and dry types).