Background The prevalence and extent of subclinical large vessel vasculopathy is not well defined among people living with HIV. We aimed to evaluate associations between aortic root and ascending aortic sizes measured by 2‐dimensional transthoracic echocardiography and HIV serostatus, and to identify risk factors for larger aortic sizes among men with HIV, including levels of circulating inflammatory markers. Methods and Results Using clinical and echocardiographic data from the MACS (Multicenter AIDS Cohort Study), adjusted multivariable linear and logistic regression was performed. Four segments of the proximal aorta were measured: aortic annulus, aortic root at the sinuses of Valsalva, sinotubular junction, and ascending aorta. HIV infection was associated with significantly larger aortic root (0.03 cm [95% CI, 0.002–0.06 cm]) and ascending aorta (0.04 cm [95% CI, 0.01–0.06 cm]) diameters. Higher standardized nadir CD4 (cluster of differentiation 4) T‐cell count was significantly associated with smaller aortic root (−0.03 cm [95% CI, −0.05 to −0.01 cm]), sinotubular junction (−0.03 cm [95% CI, −0.05 to −0.01 cm]), and ascending aorta (−0.03 cm [95% CI, −0.05 to −0.004 cm]) diameters. Higher levels of standardized TNF‐α (tumor necrosis factor‐α) were associated with larger diameters of the aortic annulus (0.02 cm [95% CI, 0.003–0.04 cm]) and sinotubular junction (0.02 cm [95% CI, 0.002–0.04 cm]). There were no other cardiovascular or HIV disease severity–related risk factors associated with the aortic dimensions. Conclusions HIV infection is an independent risk factor for greater ascending aortic sizes. Lower nadir CD4 T‐cell count and higher TNF‐α levels are associated with larger aortic sizes in men with HIV. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00046280.