AIM: To investigate the ratio of spontaneous regression of retinopathy of prematurity (ROP) and to explore the possible relevant predictive factors. METHODS: A retrospective review of 405 infants who were diagnosed with ROP and mother during pregnancy were collected. Stage, zone, and duration of ROP were recorded. Statistical analysis was performed on 51 possible predictive factors. RESULTS: Totally 356 infants showed spontaneous regression. The incidence was 100%, 95.3%, and 22.7% in stage 1, 2, and 3, respectively. The 13.4% of the ROP with plus disease eventually resolved spontaneously. All affected eyes of aggressive posterior retinopathy of prematurity (AP-ROP) failed to spontaneously regress. The mean duration of ROP was 7.2wk in patients with spontaneous resolution of ROP. Days of mechanical ventilation (OR=0.981, 95%CI, 0.965-0.997, P=0.021), retinal hemorrhage (OR=0.173, 95%CI, 0.064-0.470, P=0.001), delivery pattern (OR=2.750, 95%CI, 1.132-6.681, P=0.025), maternal anemia in pregnancy (OR=0.142, 95%CI, 0.036-0.563, P=0.005), the stages (at initial diagnosis OR=0.183, 95%CI, 0.041-0.816, P=0.026; at final diagnosis OR=0.031, 95%CI, 0.006-0.167, P<0.001), and with plus disease or not (OR=0.005, 95%CI, 0.001-0.031, P<0.001) were independent predictive factors of the spontaneous regression of ROP. CONCLUSION: Most mild ROP can spontaneously resolve. Active treatment is still recommended for stage 3 ROP, zone I ROP, AP-ROP, and ROP with plus disease. Prolonged mechanical ventilation and concurrent retinal hemorrhage reduce the likelihood of spontaneous ROP resolution. The pattern of delivery and the mother’s anemia during pregnancy can also affect the prognosis of ROP.