Purpose: To compare agreement between diagnosis of clinical level of diabetic retinopathy (DR) and diabetic macular edema (DME) derived from nonmydriatic fundus images using a digital camera back optimized for low-flash image capture (MegaVision) compared with standard seven-field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and dilated clinical examination. Subject comfort and image acquisition time were also evaluated. Subjects and Methods: In total, 126 eyes from 67 subjects with diabetes underwent Joslin Vision Network nonmydriatic retinal imaging. ETDRS photographs were obtained after pupillary dilation, and fundus examination was performed by a retina specialist. Results: There was near-perfect agreement between MegaVision and ETDRS photographs (κ=0.81, 95% confidence interval [CI] 0.73–0.89) for clinical DR severity levels. Substantial agreement was observed with clinical examination (κ=0.71, 95% CI 0.62–0.80). For DME severity level there was near-perfect agreement with ETDRS photographs (κ=0.92, 95% CI 0.87–0.98) and moderate agreement with clinical examination (κ=0.58, 95% CI 0.46–0.71). The wider MegaVision 45° field led to identification of nonproliferative changes in areas not imaged by the 30° field of ETDRS photos. Field area unique to ETDRS photographs identified proliferative changes not visualized with MegaVision. Mean MegaVision acquisition time was 9:52 min. After imaging, 60% of subjects preferred the MegaVision lower flash settings. Conclusions: When evaluated using a rigorous protocol, images captured using a low-light digital camera compared favorably with ETDRS photography and clinical examination for grading level of DR and DME. Furthermore, these data suggest the importance of more extensive peripheral images and suggest that utilization of wide-field retinal imaging may further improve accuracy of DR assessment.