Context: Recent data indicate that the secreted glycoprotein sclerostin may be involved in vascular calcification (VC). Objective: The objective of the study was to establish whether serum sclerostin levels are associated with VC in patients with rheumatoid arthritis (RA). Design: This was a cross-sectional study. Setting: The study was conducted with ambulatory care. Patients: We compared 75 RA patients with 75 age- and gender-matched control participants. Intervention: Coronary artery calcification (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography. Main Outcome Measure: Serum sclerostin levels (determined with an ELISA) were assessed. A statistical analysis was performed to identify the determinants of serum sclerostin and VC. Results: AAC and CAC were more prevalent and more severe in patients with RA than in controls. Higher levels of AAC (P = .02) and a higher lumbar bone mineral density (BMD; P = .03) were identified as independent determinants of higher serum sclerostin levels in RA patients, whereas male gender (P = .03), higher lumbar BMD (P < .0001), and low estimated glomerular rate (P < .001) were identified as determinants in controls. In RA patients, a multivariate logistic regression analysis indicated that older age [P < .01, with an odds ratio (OR) per year 1.10] and male gender (P = .02, OR 6.79) were independent determinants of CAC and that older age (P < .001, OR 1.16) were independent determinants of AAC. In controls, the independent determinants were older age (P < .01, OR 1.19), hypertension (P < .01, OR 7.31), and lumbar BMD (P = .03, OR per 30 mg/cm2 increment of 1.14) for CAC and older age (P = .01, OR 1.11) for AAC. Conclusions: Serum sclerostin levels were significantly and independently associated with AAC in RA patients.