Circulating endostatin has been linked to increased mortality, cardiovascular comorbidities, and renal impairment. However, its role as a cardiovascular risk marker in the general population remains largely unexplored. This study investigates the association between plasma endostatin and atherosclerosis, inflammation, and kidney function in a cohort of 5,026 randomly selected middle-aged individuals from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Plasma levels of endostatin, C-reactive protein (CRP), HbA1c, lipids, and creatinine were analyzed, and their associations with atherosclerosis and related markers were assessed. Coronary artery atherosclerosis was evaluated using coronary computed tomography. Blood pressure, body mass index, and waist circumference were measured, and medication use for diabetes, hyperlipidemia, and hypertension was recorded. Smoking habits were also documented. The following main results were significantly associated with endostatin. Severe coronary atherosclerosis was positively associated in men. Being on hypertensive medication or not, as reported by the participants at the interview at study inclusion, was significantly associated with endostatin. Hypertensive medication increased from 12% to 26% from the lowest to the highest quartile of endostatin. Waist circumference was positively associated, where endostatin increases, on average, 0.21±SD for a 1±SD increase of waist circumference. Kidney function, measured as eGFR, was negatively associated, where endostatin decreases, on average, 0.22±SD for a 1±SD increase in eGFR. Elevated endostatin levels were associated with advanced coronary atherosclerosis in men, antihypertensive treatment, systemic inflammation (increased CRP), increased waist circumference, and impaired kidney function (lower eGFR).