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 versus 5% natamycin indicated that the results on healing of the ulcer at 21d 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 logMAR; 95% CI, -0.30 to -0.05; P=0.006), especially in Fusarium cases (regression coefficient=-0.41 logMAR; 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.