We investigated whether dietary carotenoids lutein and zeaxanthin (L/Z) in the serum and macula were associated with central retinal arteriole and venule calibers in a follow-up ancillary study among older women in the Women's Health Initiative. METHODS.Among 390 women who participated in Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) (2016)(2017)(2018)(2019), we investigated associations between serum L/Z at Women's Health Initiative baseline (1994)(1995)(1996)(1997)(1998), and macular pigment optical density (MPOD) at CAREDS baseline (2001)(2002)(2003)(2004), with central retinal vessel caliber in CAREDS2. MPOD was measured using heterochromatic flicker photometry (0.5°from the foveal center) in CAREDS baseline and CAREDS2. Vessel calibers were measured from fundus photographs (CAREDS2). We also explored associations in women with stable MPOD (±0.10 optical density units) over 15 years (n = 106), given the long-term increases in MPOD related to diet patterns and supplement use. Associations were investigated using linear modeling. RESULTS.In the full sample (n = 390), higher serum L/Z (tertile 3 vs. 1) was positively associated with arteriole caliber (mean ± SE, 145.0 ± 1.4 μm vs. 140.8 ± 1.4 μm; P = 0.05) and venule caliber (214.6 ± 2.2 μm vs. 207.5 ± 2.2 μm; P = 0.03). MPOD was also associated with wider vessel calibers (tertile 3 vs. 1), but the trend was only statistically significant for venules (144.4 ± 1.4 μm vs. 141.1 ± 1.4 μm [P = 0.12] and 213.3 ± 2.1 μm vs. 206.0 ± 2.1 μm [P = 0.02], respectively.) Most associations were strengthened in women with stable MPOD over 15 years, including between MPOD and arteriole caliber (149.8 ± 2.6 μm vs.135.8 ± 3.0 μm; P = 0.001). CONCLUSIONS.Higher L/Z status in serum and retina was associated with larger central retinal vessel calibers. Prospective studies and clinical trials are needed to elucidate whether L/Z supplementation prevents vision loss through increasing blood flow.