The cardiometabolic syndrome (CMS) and diabetes are associated with higher cardiovascular risk. The authors compared the association of CMS risk factors and diabetes with coronary and aortic calcium. A total of 4468 adults (42% female) underwent computed tomography for determination of coronary artery calcium (CAC) and thoracic aortic calcium (TAC) and were classified according to the presence of diabetes mellitus (DM) and number of CMS risk factors. The prevalence of CAC ranged from 51% in men and 35% in women with neither DM nor CMS to 75% in men and 58% in women with both DM and CMS, whereas TAC ranged from 29% to 44% in men and 36% to 55% in women. Women with four or five CMS risk factors more often had CAC (53%) and TAC (51%) than those with DM without CMS (40% and 35%, respectively) (p<0.001 across all disease groups). Adjusted odds (and 95% confidence intervals) of CAC for those with three CMS risk factors, four CMS risk factors, DM without CMS, and DM with CMS vs. those without CMS were 1.14 (0.93-1.39), 1.46 (1.12-1.90), 1.59 (1.06-2.38), and 2.10 (1.52-2.90) for CAC and 1.14 (0.91-1.42), 1.03 (0.77-1.37), 1.03 (0.68-1.54), and 1.41 (1.03-1.92) for TAC. Multiple CMS risk factors are associated with increased CAC, but not TAC; DM with CMS has the highest prevalence of CAC and TAC.