Background: Low weight gain during the first month of life in preterm infants might be an important contributory factor for the occurrence of retinopathy of prematurity (ROP). Objective: Our study aimed to determine the effect of low weight gain on the incidence of ROP in premature infants. Patients and methods: This prospective, one-year cohort study was conducted in the Neonatology Department, in collaborate with the Ophthalmology Department in the Faculty of Medicine, Zagazig University. The study included 72 preterm neonates. Results: Out of the 72 screened infants, (41.7%) cases had ROP, among whom (35.7%) had stage I, (24.5%) had stage II (39.8%) had aggressive ROP stage III zone II, 60% had a threshold and (33.3%) with plus disease. There were statistically significant relations between ROP development and weight loss (p < 0.001), (OR, 4.5; 95% CI 0.37-54.15), prolonged duration of admission, (p < 0.005), prolonged duration of oxygen therapy (p < 0.002), respiratory distress syndrome (RDs), (p < 0.001), pneumonia (p < 0.013), bronchopulmonary dyspepsia (BPD) (p < 0.005), sepsis (p < 0.001), anemia (p < 0.001), intraventricular hemorrhage (IVH) (p < 0.005). Conclusion: Our study results suggest that low weight gain or weight loss in the first month of life may predict pre threshold ROP that requires treatment. It can help identify babies with poor periods after birth who are most at risk, also O₂ therapy, and its duration, RDs, pneumonia, sepsis, BPD, anemia, and IVH were found to be the most significant risk factors for ROP development in premature babies.