Purpose: This study aims to estimate the incidence of retinopathy of prematurity (ROP) and investigate its perinatal and neonatal risk factors in a tertiary hospital in Saudi Arabia. Methodology: This was a retrospective cohort study of premature infants admitted to a neonatal intensive care unit at a tertiary hospital in Jeddah, Saudi Arabia, from January 2016 to December 2017. Participants who met the screening criteria for ROP were included and followed up until spontaneous recovery or laser treatment. Results: A total of 119 infants screened, the incidence of ROP was 21.8% (26/119). A plus disease was diagnosed in 15.4% (4/26) of the ROP infants. For most, 80.7% (21/26) of the ROP regressed spontaneously, and 19.2% (5/26) required a laser intervention. The mean gestational age (GA) of infants diagnosed with ROP was 25.62 ± 1.58 weeks and the median birth weight (BW) 750 (interquartile range: 280) g. Lower GA, lower BW, prolonged oxygen therapy, and mechanical ventilation (MV) were significantly related to ROP disease and severity. Requiring resuscitation at birth, a lower Apgar score at 1-min, poor weight gain proportion at 6 weeks, and requiring a blood transfusion were significantly associated with ROP disease. Conclusion: Compared to other local studies, the incidence of ROP was lower in our population. Lower GA, low BW, prolonged oxygen therapy and MV, and poor weight gain at 6 weeks are well-documented risk factors. We recommend close monitoring of weight gain and oxygen therapy and modifying risk factors in preterm infants to lower the incidence and the severity of ROP.