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Retinopathy of prematurity (ROP) is one of the leading and preventable causes of blindness. The investigation of choice for diagnosing ROP is binocular indirect ophthalmoscope (BIO) done by ophthalmologists. Since the number of ophthalmologists available to do BIO examination is limited, especially in developing countries, there is a need for an alternate, cheap, reliable and feasible test. Telemedicine imaging with Digital Retinal Photography (DRP) is one such alternate diagnostic test which can be performed easily by non-ophthalmologists, with adequate training. Our objective was to conduct a systematic review to evaluate the accuracy of DRP performed by trained personnel (non-ophthalmologists) in diagnosing clinically significant ROP. Medline, EMBASE, CINAHL and Cochrane databases were searched independently by two authors. Eligible studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. Six were included in the review (three prospective; N=120, three retrospective; N=579). Studies had methodological limitations on QUADAS-2. Because of the heterogeneity of studies, data could not be pooled to derive single-effect size estimates for sensitivity and specificity. The included studies reported sensitivity of 45.5–100% with the majority being more than 90%; specificity 61.7–99.8% with the majority being more than 90%, positive predictive value 61.5–96.6% and negative predictive value of 76.9–100% for diagnosing clinically significant ROP. We conclude that diagnostic accuracy of DRP must be established in prospective studies with adequate sample size where DRP is compared against the simultaneously performed BIO examination.