Background Fungal keratitis is a rare but serious corneal disease that may result in loss of vision. The poor prognosis might be due to limited treatment option. This study aimed to evaluate the clinical efficacy of 0.25% terbinafine eye drops comparing with 5% natamycin suspension on fungal keratitis. Methods A retrospective clinical trial was performed on 90 patients presenting with direct smear and/or culture positive fungal keratitis at Beijing Tongren Hospital, Beijing, China from January 2006 to May 2008. Corneal ulcers were categorized as mild or severe. Forty-five patients were treated with topical terbinafine and the next 45 cases received topical natamycin hourly. Results Filamentous fungi were found in corneal scrapings among all 90 cases. Fungal cultures were positive in 64 patients (71%). Species of Fusarium and Aspergillus were the principal isolates. Forty (89%) patients showed favorable response to terbinafine, while forty-two (93%) patients exhibited favorable response to natamycin (P >0.05). The mean course of treatment was significantly showed in the terbinafine treatment group than natamycin group ((26.5 +/- 11.2) days versus (19.3 +/- 6.4) days; P <0.05). In terbinafine group, twenty patients with ulcers smaller than 4 mm had favorable outcome, while 20 of 25 patients with ulcers more than 4 mm in diameter had favorable response (P <0.05). Twenty-seven patients with depth of infiltration less than half of stroma thickness had favorable response to terbinafine, while 13 of 18 patients with depth of infiltration more than half of stroma responded to terbinafine. This difference was statistically significant (P<0.05). Conclusions Our findings suggest that topical terbinafine is an effective antifungal drug for the management of filamentous mycotic keratitis, particularly in cases with smaller and shallower ulcers. Its mean duration of treatment was longer than natamycin. Chin Med J 2009;122(16):1884-1888