Treatment of cutaneous leishmaniasis is often difficult. Even though most cutaneous lesions will heal spontaneously, their duration cannot be predicted in an individual case. In general, only large, multiple or diffuse lesions of the face, head and neck need to be considered for therapeutic intervention. Pentavalent antimonials (sodium stibogluconate and meglumine antimoniate) administered intralesionally or parenterally (IM or IV) are the mainstays of systemic therapy despite the toxicity associated with their use. The objective of this study was to compare the clinical efficacy of intramuscular pentavalent antimonial compound meglumine antimoniate alone and in combination with intralesional therapy in the treatment of Old World cutaneous leishmaniasis. Study was conducted as a case controlled interventional prospective study. On the basis of demonstration of Leishmania tropica (LT) bodies in the skin slit smears/skin biopsies, 60 patients with cutaneous leishmaniasis were included in the study. The patients were randomly allocated to three groups of 20 patients each: group 1 treated with intramuscular injection of meglumine antimoniate (20 mg Sb/kg/day, maximum 850 mg) for 21 days; group 2 treated with intralesional injection of meglumine antimoniate (0.5 mL, 42.5 mg of Sb) into each lesion along with intramuscular injection of meglumine antimoniate (20 mg Sb/kg/day, maximum 850 mg) for 21 days; and group 3 as a control group. The patients were followed-up for therapeutic safety and efficacy at 10, 20 and 90 days. The rate of complete cure was 55% in group 1, 75% in group 2 and 10% of spontaneous cure cases in group 3. The conclusions derived from this study are limited by the relatively small number of patients. The combination of intramuscular meglumine antimoniate along with intralesional administration of the agent is superior therapy to intralesional administration of meglumine antimoniate alone.