Hemodialysis (HD) is known to affect ocular blood flow. This case-control study aims to evaluate macular and peripapillary vasculature in patients with end-stage renal disease (ESRD) receiving HD in comparison to matched controls. A total of 24 eyes of 24 ESRD patients receiving HD and 24 eyes of 24 healthy, age- and gender-matched control subjects were prospectively included in this study. Optical coherence tomography angiography was used to image the superficial (SCP), deep (DCP), and choriocapillary (CC) macular vascular plexus, as well as the radial peripapillary capillaries (RPC) of the optic disc. In addition, retinal thickness (RT) and retinal volume (RV) were compared between both groups. Flow density (FD) values of each retinal layer and data of parameters related to the foveal avascular zone (FAZ), as well as RT and RV, were analyzed using Mann–Whitney U tests. There was no significant difference in FAZ parameters between the two groups. Whole en face FD of the SCP and CC was noticeably reduced in the HD group in comparison to the control group. FD was negatively correlated with the duration of HD treatment. RT and RV were significantly smaller in the study group than in controls. Retinal microcirculation appears altered in patients with ESRD undergoing HD. Concurrently, the DCP appears more resilient towards hemodynamic changes in comparison to the other microvascular retinal layers. OCTA is a useful, non-invasive tool to investigate retinal microcirculation in ESRD patients.