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This study assessed and validated predictors of developing clinically significant ROP (type 2 or worse) and ROP requiring treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Nationwide retrospective cohort study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included infants born between January 2014 and June 2016, admitted to level 3 neonatal intensive care units across Canada who underwent ROP screening. Data were derived from the Canadian Neonatal Network database. Predefined \u2265 1% risk for clinically significant retinopathy or prematurity and ROP requiring treatment was set as threshold for screening. Thirty-two potential predictors were analyzed, to identify and validate the most important ones for predicting clinically significant ROP. The predictors were determined on a derivation cohort and tested on a validation cohort. Multivariable logistic regression modeling was used for analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using a sample of 4,888 babies and analyzing 32 potential predictors, capturing babies with \u22651% risk of developing clinically significant ROP equated to screening babies with birth weight (BW) &amp;lt;1,300 g or gestational age (GA) &amp;lt;30 weeks while capturing babies with \u22651% risk of requiring ROP treatment equated to screening babies with BW &amp;lt;1,200 g or GA &amp;lt;29 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The Canadian ROP screening criteria can be modified to screen babies with BW &amp;lt;1,200 g or GA &amp;lt;30 weeks. 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