Purpose: The aim of this study was to quantitatively compare both the vessel density of macular capillary plexuses and the foveal avascular zone (FAZ) areas of patients receiving hydroxychloroquine (HCQ) therapy for more than 5 years while using age- and sex-matched controls. Methods: The patients undergoing HCQ who were screened for toxic effects were evaluated. The FAZ parameters included the area, perimeter, and the acircularity index. The foveal density and vessel density values of both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured using optical coherence tomography angiography (OCTA). Results: This study included 80 eyes of 40 subjects: 20 subjects in the HCQ group and 20 subjects in the control group. The FAZ perimeter and the FAZ area in the SCP and full retinal vasculature were significantly larger in the HCQ group than in the control group (p < 0.05 for all). Additionally, the vessel density of fovea in the SCP and DCP was significantly lower in the HCQ group than in the control group (p < 0.05 for all). Conclusions: OCTA provides objective documentation about FAZ and vessel density features in patients using long-term HCQ therapy before toxicity begins, and it can be used as a screening tool for detecting early changes in the macula.