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Background. Topical treatment of cutaneous leishmaniasis is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route. Recently liposomal formulations of amphotericin B have been increasingly used in the treatment of several types of leishmaniasis. Aims. The efficacy of a topical liposomal amphotericin B formulation was compared with intralesional glucantime in the treatment of cutaneous leishmaniasis. Methods. From 110 patients, the randomly selected 50 received a topical liposomal formulation of amphotericin B into each lesion, 3–7 drops twice daily, according to the lesion's size and for 8 weeks. The other group of 60 patients received intralesional glucantime injection of 1-2 mL once a week for the same period. The clinical responses and side effects of both groups were evaluated weekly during the treatment course. Results. Per-protocol analysis showed no statistically significant difference between the two groups (𝑃=0.317, 95% confidence interval (CI)=1.610 (0.632–4.101)). Moreover, after intention-to-treat analysis, the same results were seen (𝑃=0.650, 95% CI=0.1.91 (0.560–2.530)). Serious post treatment side effects were not observed in either group. Conclusions. Topical liposomal amphotericin B has the same efficacy as intralesional glucantime in the treatment of cutaneous leishmaniasis.