PURPOSE. The purpose of this study was to evaluate an automated algorithm for detecting avascular area (AA) in optical coherence tomography angiograms (OCTAs) separated into three individual plexuses using a projection-resolved technique. METHODS. A 3 x 3 mm macular OCTA was obtained in 13 healthy and 13 mild nonproliferative diabetic retinopathy (NPDR) participants. A projection-resolved algorithm segmented OCTA into three vascular plexuses: superficial, intermediate, and deep. An automated algorithm detected AA in each of the three plexuses that were segmented and in the combined innerretinal angiograms. We assessed the diagnostic accuracy of extrafoveal and total AA using segmented and combined angiograms, the agreement between automated and manual detection of AA, and the within-visit repeatability. RESULTS. The sum of extrafoveal AA from the segmented angiograms was larger in the NPDR group by 0.17 mm(2) (P < 0.001) and detected NPDR with 94.6% sensitivity (area under the receiver operating characteristic curve [AROC] = 0.99). In the combined inner-retinal angiograms, the extrafoveal AA was larger in the NPDR group by 0.01 mm(2) (P = 0.168) and detected NPDR with 26.9% sensitivity (AROC = 0.62). The total AA, inclusive of the foveal avascular zone, in the segmented and combined angiograms, detected NPDR with 23.1% and 7.7% sensitivity, respectively. The agreement between the manual and automated detection of AA had a Jaccard index of > 0.8. The pooled SDs of AA were small compared with the difference in mean for control and NPDR groups. CONCLUSIONS. An algorithm to detect AA in OCTA separated into three individual plexuses using a projection-resolved algorithm accurately distinguishes mild NPDR from control eyes. Automatically detected AA agrees with manual delineation and is highly repeatable.