Purpose The present study aimed to examine changes in optic nerve head (ONH) blood flow autoregulation in 4 quadrants (superior, nasal, inferior, and temporal) with decreased ocular perfusion pressure (OPP) during vitrectomy in order to determine whether there is a significant difference of autoregulatory capacity in response to OPP decrease at each ONH quadrant. Methods This study included 24 eyes with an epiretinal membrane or macular hole that underwent vitrectomy at Toho University Sakura Medical Center. Following vitrectomy, the tissue mean blur rate (MBR), which reflects ONH blood flow, was measured. Mean tissue MBRs in the four quadrants were generated automatically in the software analysis report. Measurements were conducted before and 5 and 10 min after intraocular pressure (IOP) elevation of approximately 15 mmHg in the subjects without systemic disorders. Results The baseline tissue MBR of the temporal quadrant was significantly lower than that of the other 3 quadrants (all P < 0.05). However, the time courses of tissue MBR in response to OPP decrease were not significantly different among the four quadrants during vitrectomy (P = 0.23). Conclusions There is no significant difference in the autoregulatory capacity of the four ONH quadrants in patients without systemic disorders during vitrectomy.