INTRODUCTION. Serum high molecular weight (HMW) adiponectin, an adipocytokine, which is a protein secreted specifically by adipose tissue, improves insulin sensitivity and plays an important role in the development of metabolic syndrome and cardiovascular disease (CVD). Pulse wave velocity (PWV) is a noninvasive method of measuring arterial stiffness for the assessment of CVD in high-risk populations. We investigated whether serum HMW adiponectin is independently associated with arterial stiffness when evaluated using PWV. METHODS. We randomly recruited 99 men aged 69 ± 9 (mean ± standard deviation) years and 170 women aged 68 ± 7 years during their annual health examination in a single community. Peripheral arterial stiffness was evaluated by mean PWV determined at three points: from the heart to the carotid artery, to the brachial artery, and to the ankle. RESULTS AND CONCLUSIONS. Age-adjusted PWV in all sites other than the heart to the carotid artery decreased progressively with increased serum HMW adiponectin. Age-adjusted mean PWV significantly decreased from the lowest to the highest serum HMW adiponectin group. Multiple linear regression analyses for mean PWV revealed that decreased serum HMW adiponectin levels were significantly associated with increased mean PWV as well as age, BMI, SBP, DBP, prevalence of antihypertensive medication, and eGFR. Inclusion of serum HMW adiponectin into the model further increased the coefficient of determination (R(2)). Multivariate-adjusted mean PWV was significantly lowest in the highest serum HMW adiponectin group.