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Introduction: Arterial stiffness is widely used as an index of arteriosclerosis and is associated with cardiovascular disease (CVD). Recently, cardio-ankle vascular index (CAVI) was developed as a measurement of arterial stiffness that is independent of blood pressure at the time of arterial stiffness evaluation. The associations of CAVI with CVD events and all-cause mortality have not been extensively assessed. We therefore systematically reviewed the studies reporting CAVI and relevant outcomes.Methods: We searched for both prospective and cross-sectional studies using MEDLINE, Embase, and Cochrane from inception to April 11, 2017. Two independent reviewers screened the retrieved papers, extracted relevant data and assessed the risk of bias. Any discrepancy was solved by discussion or a third reviewer. Heterogeneity among studies was assessed using the I2 statistic. We pooled the results of studies that were sufficiently homogeneous.Results: Among 1,519 records, we identified 9 cohort studies (n=5,292) and 17 cross-sectional eligible studies (n=7,309). All 9 cohort studies reported the outcome of composited CVD (498 cases), but the categorization/modeling of CAVI was not consistent across those studies. The pooled hazard ratio (HR) of CVD for the highest vs. lowest CAVI category in 3 studies was borderline significant (pooled HR=1.34 [0.95, 1.87], p=0.092) (I2= 25.2%, p=0.263). For 3 studies examining the continuous association between CAVI and CVD, 1standard deviation (SD) increment of CAVI was significantly associated with CVD risk (pooled HR=1.22 [1.03, 1.45], p=0.023) (I2= 27.1%, p=0.253). Only 3 cohort studies investigated CAVI and all-cause mortality, and none of them reported a significant association. All 17 cross-sectional studies reported higher CAVI values in patients with CVD compared to those without CVD, with statistical significance in most studies.Conclusions: CAVI was generally higher in patients with CVD compared to their counterparts. In terms of the prospective prognostic value of CAVI, we found a limited number of studies, but they indicated a modest association between CAVI and CVD risk. Our systematic review highlighted the need for large prospective studies to assess the usefulness of CAVI as a predictor of CVD and mortality.