To evaluate the efficacy of a short course of a lipid formulation of amphotericin B (L-AmB) for the treatment of Mediterranean visceral leishmaniasis (VL), an open prospective study was conducted. Forty-one children with parasitologically confirmed leishmaniasis received L-AmB, 10 mg/kg daily for 2 days. The comparison groups were 30 children who, in a previous study, were treated with L-AmB, 4 mg/kg daily for 5 days, and 52 children who were treated with meglumine antimoniate. At 6 months after completion of treatment, overall treatment success was noted for 40 of 41 children treated with 2 doses of L-AmB, 27 of 30 children treated with 5 doses of L-AmB, and 47 of 52 children treated with meglumine antimoniate. Abatement of fever, reduction in spleen size, and correction of laboratory parameters occurred more quickly among the children who received 2 doses of L-AmB than among the comparison groups, and the total estimated cost of the 2-dose regimen was also lower than that of the other regimens. Two doses of L-AmB, 10 mg/kg each, is cost-effective therapy for Mediterranean VL in children.