The purpose of the study was to determine whether monoscopic photography could serve as an accurate tool when used to screen for clinically significant macular edema. In a masked randomized fashion, two readers evaluated monoscopic and stereoscopic retinal photographs of 100 eyes. The photographs were evaluated first individually for probable clinically significant macular edema based on the Early Treatment Diabetic Retinopathy Study criteria and then as stereoscopic pairs. Graders were evaluated for sensitivity and specificity individually and in combination. Individually, reader one had a sensitivity of 0.93 and a specificity of 0.77, and reader two had a sensitivity of 0.88 and a specificity of 0.94. In combination, the readers had a sensitivity of 0.91 and a specificity of 0.86. They correlated on 0.76 of the stereoscopic readings and 0.92 of the monoscopic readings. These results indicate that the use of monoscopic retinal photography may be an accurate screening tool for clinically significant macular edema.