Introduction: Cardiovascular risk factors are associated with increased risk of future cancer. However, the relationship between quantitative parameters of atherosclerosis and the risk of future cancer is unclear. Here we investigated the association between cardio-ankle vascular index (CAVI), an indicator of arterial stiffness, and future new cancer diagnosis in patients with coronary artery disease. Methods: This was a prospective observational study which enrolled consecutive 1122 patients with coronary artery disease, excluding patients with atrial fibrillation or dialysis. According to the receiver operating characteristic curve analysis, the cut-off value of CAVI in predicting new cancer diagnosis was 8.70. We divided patients into two groups: the high-CAVI group (CAVI ≥ 8.70, n = 578, 51.6%) and the low-CAVI group (CAVI < 8.70, n = 544, 48.4%). We compared the patients’ characteristics and followed the incidence of new cancer diagnosis. Results: The high-CAVI group, as compared with the low-CAVI group, were older (72.3 vs. 64.0 years, P < 0.001) and had higher prevalence of diabetes mellitus (53.8 vs. 45.6%, P = 0.006), chronic kidney disease (47.1 vs. 32.5%, P < 0.001) and anemia (46.0 vs. 32.9%, P < 0.001). In contrast, there was no difference in the prevalence of smoking, hypertension, dyslipidemia, heart failure and history of malignancies between two groups. In the follow up period (mean of 2182 days), there were 141 new cancer diagnosis. The cumulative incidence of new cancer diagnosis was significantly higher in the high-CAVI group than in the low-CAVI group ( P = 0.007). In the multivariable Cox proportional hazard analysis after adjusting for confounding factors, CAVI was found to be an independent predictor of new cancer diagnosis (hazard ratio 1.51, 95% confidence interval 1.05-2.17, P = 0.022). Conclusions: High CAVI is associated with the risk of future cancer in patients with coronary artery disease.