The effectiveness of systemic treatment for Leishmania tropica cutaneous leishmaniasis (CL) remains unclear. The purpose of the study is to evaluate the efficacy and safety of systemic treatments available against L. tropica CL. This retrospective study was performed in 114 patients. Systemic treatments included liposomal amphotericin B (L-AmB) and sodium stibogluconate (SSG). One hundred and fourteen patients underwent systemic treatment for L. tropica CL. Favorable treatment responses were recorded in 72.5% and 70.2% of the patients in the L-AmB and SSG groups, respectively; 25.3% and 46% of those in the L-AmB and SSG groups respectively, experienced at least one adverse effect. Lesions in cartilaginous areas were associated with higher treatment failure. Prior topical or systemic treatment increased the chance of future systemic treatment success. L-AmB was associated with a shorter IV treatment duration and a better safety profile. Thus, L-AmB is the treatment of choice for L. tropica CL.