PURPOSE: To assess the baseline differences and longitudinal rate of change in retinal and choroidal imaging parameters between apolipoprotein ε4 (APOE ε4) carriers and noncarriers with normal cognition. DESIGN: Prospective study. SUBJECTS: Four hundred thirteen eyes of 218 individuals with normal cognition aged ≥ 55 years with known APOE status (98 APOE ε4 carriers and 120 noncarriers). The exclusion criteria included diabetes mellitus, uncontrolled hypertension, glaucoma, and vitreoretinal or neurodegenerative disease. METHODS: OCT and OCT angiography (OCTA) were performed at baseline and 2 years (Zeiss Cirrus HD-OCT 5000 with AngioPlex; Zeiss Meditec). The groups were compared using sex- and age-adjusted generalized estimating equations. MAIN OUTCOME MEASURES: OCT parameters: retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness (CST), and choroidal vascularity index. OCT angiography parameters: foveal avascular zone area, perfusion density (PD), vessel density, peripapillary capillary PD (CPD), and capillary flux index (CFI). The rate of change per year was calculated. RESULTS: At the baseline, the APOE ε4 carriers had lower CST (P = 0.018), PD in the 6-mm ETDRS circle (P = 0.049), and temporal CFI (P = 0.047). Seventy-one APOE ε4 carriers and 78 noncarriers returned at 2 years; at follow-up, the 6-mm ETDRS circle (P = 0.05) and outer ring (P = 0.049) showed lower PD in the APOE ε4 carriers, with no differences in the rates of change between the groups (all P > 0.05). CONCLUSIONS: There was exploratory evidence of differences in the CST, PD, and peripapillary CFI between the APOE ε4 carriers and noncarriers with normal cognition. Larger and longer-term studies may help further elucidate the potential prognostic value of these findings.