Context: Acromegaly increases cardiovascular morbidity. We tested the hypothesis that increased arterial stiffness together with left ventricular hypertrophy may be a contributory factor. Patients and Design: Fifty-six patients (40 males, 54 ± 13 yr; 25 active disease, 31 in remission) and 46 healthy controls (30 males, 52 ± 13 yr) underwent measurements of aortic pulse wave velocity (PWV), carotid Doppler (IMT), echocardiography, and cardiovascular risk factors. Results: Mean serum IGF-I was 323 ± 286 ng/ml (SD score 1.8 ± 1.9) in all patients. Age, body mass index, diastolic blood pressure (BP), and lipid levels were similar comparing patients and controls. Systolic BP (130.8 ± 19.9 vs. 122 ± 14 mm Hg controls, P <0.01) and PWV (11.7 ± 3.8 vs. 9.7 ± 2.8 m/sec, 95% confidence interval -3.4 to -0.7, P <0.01) were higher in patients than controls. Regression analysis revealed age, presence of acromegaly, systolic BP, and body mass index, inversely, as significantly and independently associated with PWV. No difference in carotid IMT was seen (0.8 ± 0.2 patients vs. 0.7 ± 0.2 mm controls, P = 0.5) or between active/controlled disease. In the subset of participants with echocardiography (n = 32), left ventricular mass was higher by a mean of 38.2 g (95% confidence interval -80.9 to -4.6, P = 0.08). Conclusion: In summary, patients with acromegaly had independently and significantly increased aortic PWV as evidence of arterial stiffening but unaltered carotid IMTcomparedwith controls, also influenced by age and systolic BP. Premature cardiovascular disease in patients with acromegaly likely related to pressure-related arterial and left ventricular stiffening rather than atherosclerotic disease. Copyright © 2011 by The Endocrine Society.