AIM:To evaluate the role of umbilical cord blood serum (CBS) therapy in cases with persistent corneal epithelial defects (PED).METHODS:Sixteen eyes of 14 patients with PED who were resistant to conventional treatment were treated with 20% umbilical cord serum eye drops. Patients were followed-up weekly until epithelization was complete. The collected data included the grade of corneal lesion (Grade I:epithelial defect+superficial vascularization, Grade II:epithelial defect+stromal edema, Grade III:corneal ulcer+stromal melting), the size of epithelial defect (pretreatment, 7^th, 14^th and 21^st days of treatment), and follow-up time was evaluated retrospectively.RESULTS:The mean size of epithelial defect on two perpendicular axes was 5.2×4.6-mm² (range:2.5-8×2.2-9 mm²). Mean duration of treatment was 8.3±5wk. CBS therapy was effective in 12 eyes (75%) and ineffective in 4 eyes (25%). The epithelial defects in 4 ineffective eyes were healed with amniotic membrane transplantation and tarsorrhaphy. The rate of complete healing was 12.5% by 7d, 25% by 14d, and 75% by 21d. The healing time was prolonged in Grade III eyes in comparison to eyes in Grade I or Grade II.CONCLUSION:The results of the current study indicated the safety effectiveness of CBS drops in the management of PED. The grade of disease seems have a role on the healing time.