Aims To develop a new national screening guideline for retinopathy of prematurity (ROP). Methods Included were infants of the 2009 prospective ROP inventory in The Netherlands with gestational age (GA) <32weeks and/or birth weight (BW) <1500g. Five models were studied, based on GA and BW in combination with no, one or a set of five risk factors for ROP. Risk factors were determined by logistic regression. In MEDLINE and EMBASE, additional risk factors were searched. A precondition was that no infants with severe ROP would be missed. Receiver operating characteristic curves or classical meas Results The model including all infants with severe ROP comprised screening of infants with GA <30weeks and/or BW <1250g and a selection of infants with GA 30-32weeks and/or BW 1250-1500g, with at least one of the following risk factors: artificial ventilation (AV), sepsis, necrotising enterocolitis (NEC), postnatal glucocorticoids or cardiotonica. This model would not detect 4.8% (95% CI 2.5% to 8.0%) of infants with mild ROP and would reduce infants eligible for screening by 29%. Conclusions In The Netherlands, screening may be safely reduced using a new guideline based on GA, BW, AV, sepsis, NEC, postnatal glucocorticoids and cardiotonica.