Abstract: BACKGROUND: Retinopathy of prematurity is a major cause of morbidity in preterm infants but population-based studies to evaluate recent trends in incidence in the United States (US) are lacking. Moreover, previous studies did not include the use of anti-Vascular Endothelial Growth Factor medications. The objective was to examine the recent secular trends in the incidence and treatment of severe retinopathy of prematurity (sROP) in the United States (US) from 2009 to 2018. METHODS: This was a population-based, serial cross-sectional study that utilized data from the National Inpatient Sample. The inclusion criteria were preterm infants with gestational age (GA) ≤30 weeks and length of stay > 28 days. The primary outcomes were trends in ROP surgery (photocoagulation, cryotherapy, scleral buckling, vitrectomy) and intravitreal injection of therapeutic (anti-VEGF) medications. The Cochrane-Armitage test was used to evaluate trends and P-value < 0.05 was considered significant. RESULTS: Out of 279,664 hospitalizations that met the inclusion criteria, 12,942 (4.6%) had sROP. Those with sROP were more likely to have severe intraventricular hemorrhage (12.5% vs 6.1%), bronchopulmonary dysplasia (48.2% vs 25.9%), and pulmonary hypertension (10.7% vs 4.7%). From 2009–2018, sROP significantly increased from 3.4% to 5.3% (P < 0.001), ROP surgery decreased from 36.8% to 11.9% (P < 0.001) while intra-vitreal administration of therapeutic drugs increased from 2% to 7.6% (P < 0.001). CONCLUSION: Surgery for sROP decreased while intra-vitreal administration of therapeutic drugs increased in the setting of increasing incidence of sROP in the US. Taken together, these findings suggest a gradual practice change and the long-term outcomes of intra-vitreal agents warrants future study.