ABSTRACT: Importance:Most premature infants will not develop retinopathy of prematurity (ROP) of clinical relevance, yet screening evaluations often continue beyond hospital discharge, even for those infants without ROP. Objectives:To identify the characteristics of infants at low risk for ROP, for whom further postdischarge screening may be of limited value. Design, Setting, and Participants:This study took place in North American neonatal intensive care units where clinicians had expertise in ROP. Infants with birth weight less than 1251 g who were born at or transferred into an Telemedicine Approaches to Evaluating Acute-Phase ROP (e-ROP) study center were enrolled. The study included post hoc analysis of prospectively collected in-hospital ROP examination results among infants enrolled in the e-ROP study. We characterized infants without ROP and performed logistic regression on the subset of infants who were 27 to 33 weeks' gestational age to determine characteristics associated with the absence of ROP during all in-hospital examinations. Main Outcomes and Measures:The main measure was the absence of ROP prior to hospital discharge; the main outcome was treatment for ROP. Results:A total of 1257 infants born at 22 to 35 weeks' gestation (median [interquartile range (IQR)], 26 [25-28] weeks) with birth weights less than 1251 g (median [IQR], 860 [690-1040] g) underwent 4113 ROP examinations between 31 and 47 weeks' postmenstrual age. Overall, 1153 examinations (38%) showed no ROP, and 456 infants (36%) did not have ROP prior to study center discharge or study end point. Among infants without ROP during examinations at 32 and 33 weeks' postmenstrual age, 16 (9.4%) and 14 (5.3%) subsequently underwent ROP treatment, respectively. At hospital discharge, there was no ROP in 59% of infants of 27 to 33 weeks' gestational age, compared with 15% of those who were less than 27 weeks' gestational age (difference, 44% [95% CI, 38.5%-48.1%]; P???.001). With more than 85% follow-up among infants without ROP by 37 weeks' postmenstrual age, none (95% CI, 0%-0.98%) were treated for ROP. In multivariate analysis of infants born at 27 to 33 weeks' gestation, larger birth weight (OR, 4.1 [95% CI, 1.6-10.3]) and higher gestational age (OR, 4.0 [95% CI, 1.5-10.8]) were significantly associated with absence of ROP. Conclusions and Relevance:These findings suggest that, for infants of 27 weeks' gestational age or greater and birth weights larger than 750 g, if no ROP has been detected by discharge at near-term postmenstrual age, then further ROP surveillance has limited value. Studies of all infants at risk are needed to develop more specific, objective criteria for termination of ROP surveillance and focus resources on infants at higher risk of ROP. Trial Registration:ClinicalTrials.gov Identifier: NCT01264276.