AIM: To review published clinical studies examining the effect of natamycin in the treatment of fungal keratitis.METHODS: We selected the publications in CENTRAL,MEDLINE, EMBASE, CNKI, and CBM. This study systematically reviewed published randomized controlled trials(RCTs) that compared natamycin to other antifungal agents, and conducted feasible Meta-analysis of efficacy results using Revman 5.2 software.RESULTS: We included seven trials which were mainly carried out in developing countries of Asia, with five trials conducted in India, one each in China and Bangladesh. A total of 804 participants were randomized to following comparisons: 2% econazole versus 5%natamycin showed little difference in the effects of treatment of fungal keratitis [RR =0.99, 95% confidence interval(CI), 0.8 to 1.21]; chlorhexidine gluconate versus5% natamycin indicated that the results on healing of the ulcer at 21 d was less conclusive(RR=0.77, 95% CI, 0.55 to 1.08; I2=0%); 1% voriconazole versus 5% natamycin suggested that natamycin treatment appeared to be significantly better outcomes than voriconazole(regression coefficient =-0.18 log MAR; 95% CI,-0.30 to-0.05; P =0.006), especially in Fusarium cases(regression coefficient=-0.41 log MAR; 95% CI,-0.61 to-0.20; P 【0.001);natamycin versus fluconazole showed a significant difference in cure rate(χ2=5.048, P 【0.05) and natamycin group was more effective than fluconazole in average period of therapy(t =7.94, P 【0.01).CONCLUSION: Natamycin was a preferable choice in the treatment of fungal keratitis, especially in the early period of Fusarium cases.