Purpose: To investigate and compare the efficacy of autologous serum eye drops with amniotic membrane transplantation in eyes with neurotrophic corneal ulcers. Methods: In this retrospective study, 42 eyes of 42 patients (30 females and 12 males) with neurotrophic corneal ulcers were included and divided into group I (n = 20) who were treated with autologous serum eye drops and group II (n = 22) who underwent amniotic membrane transplantation. The epithelial healing time and best corrected visual acuity were performed before and after treatments. Results: In group I, the mean age was 57.1 ± 10.1 years; and at the end of 6.7 ± 2.05 months follow up, 14 (70%) of 20 eyes healed completely with a minimal scarring and vascularization. Two patients had persistent epithelial defects, four patients healed incomplete because of deep stromal ulcers in eyes with post-herpes neurotrophic ulcers. In group II, the mean age was 58.7 ± 14.7 years. Seventeen eyes (72.7%) of 22 patients healed completely and there was no recurrence in these patients at the 6.8 ± 3.9 months follow-up period. Two incomplete healed patients had persistent epithelial defects caused by HSV and the other three patients had deep stromal ulcers caused by the abuse of topical anesthetics. The mean epithelialization time was 22.1 ± 8.0 days in group I and 20.0 ± 4.64 days in group II. In group I, best corrected visual acuity improved in 18 of 20 (90%) eyes and 17 of 22 (77.2%) eyes in group II. Conclusions: Both autologous serum eye drops and amniotic membrane transplantation are effective for eyes with neurotrophic corneal ulcers because of many epitheliotrophic factors. Also, we observed that multilayered amniotic membrane transplantation is more effective than autologous serum in deep corneal ulcers with postherpes neurotrophic keratitis in our cases.