Background Impaired coronary endothelial function (CEF) predicts cardiovascular events and occurs in people living with HIV (PLWH). Women compared with men living with HIV have worse cardiovascular outcomes, but prior CEF studies included few women. The authors aimed to compare CEF in women with HIV versus without HIV, investigate sex differences in CEF and PCSK9 (proprotein convertase subtilisin/kexin type 9) (a proinflammatory biomarker), and evaluate whether increased serum levels of PCSK9 are associated with CEF in PLWH. Methods and Results Magnetic resonance imaging was performed to measure CEF (as percent change in coronary cross‐sectional area and coronary blood flow during isometric handgrip exercise, an endothelial‐dependent stressor) and serum PCSK9 levels were measured in 106 PLWH and 76 people without HIV. CEF was significantly reduced in women with versus without HIV (cross‐sectional area change −0.5%±9.7 versus 9.5%±3.2, respectively). After adjustment for age, body mass index, and menopausal status, women with HIV still had reduced CEF (percentage of cross‐sectional area: ß −8.3 [−13 to −3.6], P=0.001) compared with women without HIV. PCSK9 was elevated in women living with HIV versus without (306 ng/mL [200–412 ng/mL] versus 180 ng/mL [154–223 ng/mL], P