Purpose To examine the macular microstructure in macular edema (ME) due to retinal vein occlusion (RVO) in terms of ischemic or nonischemic type to determine whether and how ischemia affects macular microstructure. Methods This retrospective, nonrandomized study included 75 newly diagnosed RVO cases (group 1: 55 nonischemic RVO cases and group 2: 20 ischemic RVO cases) with evidence of center-involving ME without any treatment. Quantitative measures on spectral-domain optical coherence tomography images were performed. Central subfield thickness (CST) was collected in the central 1 mm from the thickness map. The following items were evaluated in a 3-mm-wide area (perifoveal ETDRS circle) centered on the fovea: disorganization of the retinal inner layers (DRIL), disrupted external limiting membrane (ELM) and ellipsoid zone disruption (EZD). The microstructural changes were measured manually. Results Baseline characteristics, such as age, sex, study eye, and RVO risk factors, were similar between the groups (P > 0.05). CST was 554.15 +/- 191.45 mu m for group 1 and 769.90 +/- 290.00 mu m for group 2 (P: 0.001). The extent of DRIL was 1864.09 +/- 941.70 mu m and 2447.25 +/- 492.59 mu m for groups 1 and 2, respectively (P: 0.010). The disrupted ELM length was 1700 (0-3000) mu m for group 1 and 2725 (300-3000) mu m for group 2 (P: 0.027). The EZD length was 1453.09 +/- 870.38 mu m for group 1 and 1846.00 +/- 926.54 mu m for group 2 (P: 0.093). Conclusions Ischemic RVOs cause greater macular edema and greater disruption in the macular microstructure compared to nonischemic RVOs, especially in terms of DRIL and ELM.