IMPORTANCE: The Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study showed that the addition of postnatal weight gain to birth weight and gestational age detects similar numbers of infants with ROP, but requires examination of fewer infants. OBJECTIVE: To determine the incremental cost-effectiveness of screening with G-ROP compared with conventional screening. DESIGN, SETTING AND PARTICIPANTS: We built a microsimulation model of a 1-year US birth cohort <32 weeks gestation, using data from the G-ROP study. We obtained resource utilization estimates from the G-ROP dataset and from secondary sources, and test characteristics from the G-ROP cohort. RESULTS: Among 78,281 infants nationally, screening with G-ROP detected ~25 additional infants with Type 1 ROP. This was accomplished with 36,233 fewer examinations, in 14,073 fewer infants, with annual cost savings of approximately US$2,931,980 through hospital discharge. CONCLUSIONS: Screening with G-ROP reduced costs while increasing the detection of ROP compared with current screening guidelines.