Zinc sulfate (ZS) has been used for the treatment of acute cutaneous leishmaniasis (CL) in both forms of in vivo and in vitro recently. The aim of the present study was to compare the efficacy of intralesional injection of ZS 2% solution with intralesional glucantime in the treatment of acute CL. In this double-blind randomized clinical trial, 80 cases with acute old world dry type CL were enrolled in the study. The treatment protocol in the first group consisted of intralesional injection of ZS 2% vials once a week for 10weeks or sooner in case of complete resolution of the lesions. In the second group, intralesional glucantime once a week for 10weeks or sooner in case of complete resolution of the lesions were used. In both groups cryotherapy was performed once every other week for 10weeks. In ZS versus second group, partial and complete clinical response was observed with fewer injections although this difference was not statistically significant. In addition, we found that the trend of treatment in second group was faster but again it was not significant [partial treatment: hazard ratio (HR) 1.4, 95% CI 0.7-2.9; complete treatment: HR 1.3, 95% CI 0.6-2.8]. The results of this study showed that the intralesional injection of ZS 2% solution was as effective as glucantime on the healing of the acute old world dry type CL.