Purpose: To compare Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels between two digital fundus imaging protocols for research studies of diabetic retinopathy: thed standard 7-field (7F) imaging and the more recent 4-widefield (4W) imaging. Methods: Two hundred twenty-two participants enrolled in the Diabetes Prevention Program Outcomes Study underwent concurrent 7F and 4W imaging. The ETDRS levels from 220 paired gradable images were determined by masked graders. Each image was graded by two independent graders with adjudication by a senior grader, if necessary. Percent agreement between graders and between imaging protocols was evaluated with kappa statistics and weighted kappa statistics. Results: Of 220 gradable eyes, diabetic retinopathy was seen in 11.8%; this was mild in 10.4% and more than mild in 1.4% using 7F imaging. The ETDRS levels showed exact agreement of 95% between 7F and 4W imaging (weighted kappa 0.86). Intergrader agreement for each modality had exact agreement of 89% (weighted kappa of 0.73) for 7F and 91% (weighted kappa 0.77) for 4W. Conclusions: There is substantial agreement in the ETDRS severity level between the 7F and 4W digital imaging protocols, demonstrating that the two imaging protocols are interchangeable. Both 4W and 7F digital imaging protocols can be used for assessing ETDRS levels, even in populations with minimal diabetic retinopathy. Translational Relevance: The 4W protocol requires fewer images than the 7F, is more comfortable for the patients, is easier for photographic capture, and provides diabetic retinopathy data that is equivalent to the 7F imaging protocol.