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Purpose: To evaluate the influence of systemic factors on macular vessel density in quantitative Optical Coherence Tomography Angiography (OCTA) by sex. Study design: A cross-sectional study. Methods: A total of 2018 adults were recruited in this study. Participants were excluded (n=964) due to missing data, eye-related problems, or low OCTA scan quality. Macular vessel densities were measured with OCTA using split-spectrum amplitude decorrelation angiography algorithm. Only the data from the right eyes were selected for analysis. Multivariable linear regression analysis was performed to determine the associations between macular vessel density and obesity-related systemic factors in each gender group. Results: The right eyes of 1054 participants (59.6% women) were enrolled. Men had significantly higher obesity parameters and associated risk factors. In multivariable linear regression analysis in men, older age and type 2 diabetes mellitus were independently associated with lower superficial retinal vessel density (β = −0.37, p = 0.002; β = −1.22, p = 0.03) and deep retinal vessel density, respectively (β = −0.66, p < 0.001; β = −1.76, p = 0.02); positive association was also observed between body mass index (BMI) and superficial retinal vessel density (β = 0.56, p = 0.02). In women, only higher systolic blood pressure was independently associated with a lower deep retinal vessel density (β = −0.50, p = 0.003). Conclusions: This large cross-sectional study shows that older age and type 2 diabetes mellitus are associated with lower superficial and deep retinal capillary vessel density in men. This may help clinicians better understand how systemic factors influence retinal vessel density in different genders and future studies can ascertain more potential sex differences. [ABSTRACT FROM AUTHOR]