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Studies report conflicting associations between preeclampsia and retinopathy of prematurity (ROP). This study provides explanations for the discrepancies to clarify the relationship between preeclampsia and ROP.To evaluate the association of maternal preeclampsia and risk of ROP among infants in an unrestricted birth cohort and a restricted subcohort of preterm, very low birth weight (P-VLBW) infants.A retrospective review of 290 992 live births within the Intermountain Healthcare System in Utah from January 1, 2001, through December 31, 2010, was performed. Generalized estimating equations for logistic regressions with covariate adjustment were applied to relate ROP to preeclampsia among the full cohort and in a subcohort of P-VLBW infants born at younger than 31 weeks’ gestation and weighing less than 1500 g.The occurrence of ROP was related to maternal preeclampsia in the full cohort and in a subcohort of P-VLBW infants.In the full cohort, 51% of the infants were male and the mean (SD) gestational age was 38.38 (1.87) weeks. In the P-VLBW cohort, 55% were male and the mean (SD) gestational age was 26.87 (2.40) weeks. In the full cohort, preeclampsia was associated with an increased risk of all ROP (adjusted odds ratio [aOR], 2.46; 95% CI, 2.17–2.79; P < .001), severe ROP (aOR, 5.21; 95% CI, 3.44–7.91; P < .001), infant death (aOR, 1.66; 95% CI, 1.16–2.38; P = .006), and giving birth to a P-VLBW infant (aOR, 7.74; 95% CI, 6.92–8.67; P < .001). In the P-VLBW subcohort, preeclampsia was inversely associated with the development of all ROP (aOR, 0.79; 95% CI, 0.68–0.92; P = .003), severe ROP (aOR, 0.62; 95% CI, 0.36–1.06; P = .08), and infant death (aOR, 0.19; 95% CI, 0.11-0.32; P < .001).Preeclampsia was associated with an increased risk of developing ROP among an unrestricted cohort but with a reduced risk of ROP among a restricted subcohort of P-VLBW infants. Although the conflicting associations in the full and P-VLBW cohorts may reflect true differences, the association of a reduced risk of ROP among the P-VLBW subcohort also may reflect biases from restricting the cohort to prematurity, because prematurity is an outcome of preeclampsia.