OBJECTIVES: To compare the cost-effectiveness of alternative methods of screening for retinopathy of prematurity (ROP) in the United Kingdom, including the existing method of indirect ophthalmoscopy by ophthalmologists and digital photographic screening by nurses. METHODS: A decision tree model was used to compare five screening modalities for the UK population of preterm babies, using a health service perspective. Data were taken from published sources, observation at a neonatal intensive care unit (NICU), and expert judgment. RESULTS: We estimated that use of standard digital cameras by nurses in NICUs would cost more than current methods (pound 371 compared with pound 321 per baby screened). However, a specialist nurse visiting units with a portable camera would be cheaper (pound 172 per baby). These estimates rely on nurses capturing and interpreting the images, with suitable training and supervision. Alternatively, nurses could capture the images then transmit them to a central unit for interpretation by ophthalmologists, although we estimate that this would be rather more expensive (pound 390 and pound 201, respectively, for NICU and visiting nurses). Sensitivity analysis was used to examine the robustness of estimates. CONCLUSIONS: It is likely that there is an opportunity to improve the efficiency of the ROP screening program. We estimate that screening by specialist nurses trained in image capture and interpretation using portable digital cameras is a cost-effective alternative to the current program of direct visualization by ophthalmologists. This option would require the development of a suitable portable machine. Direct comparative research is strongly needed to establish the accuracy of the various screening options.