Background: Some treatment reported for cutaneous leishmaniasis. The studies examined the impact of the paromomycin has different characteristics and results. The aim of the present study was to conduct a systematic review and meta-analysis of all randomized clinical trials evaluating the effectiveness of paromomycin in the treatment of cutaneous leishmaniasis in Iran.Methods: Literature search was conducted using MEDLINE, Web of Science, Scopus, Scientific Information Database, IranMedex, Magiran, Iranian Registry of Clinical Trials (from February 2000 to May 2016), and references cited in the text of selected studies. Search terms used were “paromomycin”, “cutaneous leishmaniasis”, “randomized”,” aminosidine”, “controlled trial”, and “clinical trial”. Random effects models were used to calculate the measure of association, with 95% confidence intervals, to analyze the efficacy of paromomycin in the treatment of cutaneous leishmaniasis.Results: Initial search yielded 76 citations. Of these original results, 9 met our specific selection criteria. Four of the randomized controlled trials compared the efficacy of paromomycin in the treatment of cutaneous leishmaniasis with that of a placebo; they were included in the meta-analysis. The success rate of treatment with paromomycin was higher than that with the placebo (pooled RR=4.50, 95% CI: 2.54 to 8.02; P=0.001 and I2=26.7%), whereas the difference with the non-placebo treatments was nonsignificant (pooled RR=0.79, 95% CI: 0.58 to 1.073; P=0.131 and I2=83.3%).Conclusion: No significant difference was observed between paromomycin and the other treatments in their effectiveness in the treatment of cutaneous leishmaniasis. Because no single drug is effective against all the forms of leishmaniasis, we suggest multidrug therapy.