Retinopathy of prematurity (ROP) represents a leading cause of childhood blindness. The purpose of our study was to evaluate incidence, trends in cost and length of hospital stay, and risk factors for ROP using a publicly available population-based dataset, the National Inpatient Sample. This cross-sectional study analyzed data from 2009 to 2018 using the National Inpatient Sample. Premature neonates (n= 717 277) who met the screening criteria for ROP with gestational age of ≤ 30 weeks or birthweight (BW) of ≤ 1500 g were identified. Database analysis. Incidence, demographics, risk factors for ROP development, trends in cost, and length of stay were evaluated. In total, incidence of ROP increased from 11% in 2009 to 15% in 2018 (P < 0.001). Multivariate logistic regression model of ROP development showed its associations with female sex (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.10-1.17), Hispanic (OR, 1.10; 95% CI, 1.03-1.18), and Black (OR, 0.91; 95% CI 0.86-0.96) ethnicity. Neonates with lower BWs, particularly those in the 500- to 999-g subgroup (OR, 2.64; 95% CI, 2.44-2.85) and younger gestational ages, particularly those born between 25 and 28 weeks gestational age (OR, 2.41; 95% CI, 2.25-2.58), had increased risk of developing ROP. Comorbidities associated with the development of ROP were perinatal jaundice (OR, 1.84; 95% CI, 1.74-1.94), patent ducts arteriosus (OR, 1.67; 95% CI, 1.60-1.75), intraventricular hemorrhage (OR, 1.41; 95% CI, 1.35-1.48), perinatal infection (OR, 1.84; 95% CI, 1.74-1.94), and respiratory distress syndrome (OR, 1.05; 95% CI, 1.01-1.10). Retinopathy of prematurity develops in about 1 of 10 premature infants and incidence has been shown to be increasing. Significant risk factors were female sex, Hispanic ethnicity, lower BW, younger gestational age, and systemic comorbidities, including perinatal jaundice, patent ductus arteriosus, intraventricular hemorrhage, perinatal sepsis, and respiratory distress syndrome. Proprietary or commercial disclosure may be found after the references.