Detection of masked uncontrolled hypertension (MUCH) that was defined for treated hypertensive individuals who had normal office blood pressure (BP) but elevated ambulatory BP remains largely challenging. Arterial stiffness is one of the leading risk markers for hypertension and can be clinically assessed by the cardio-ankle vascular index (CAVI). This study aimed to evaluate the association between CAVI and MUCH. A total of 155 hypertensive patients were included with their office BP levels and ambulatory BP monitoring measurements, which were divided into controlled hypertension (CH), MUCH, and sustained uncontrolled hypertension (SUCH) groups, respectively. There were 48 patients with CH, 56 patients with MUCH, and 51 patients with SUCH. Both MUCH and SUCH groups had a significantly higher CAVI than the CH group (9.05 (8.20-9.91) vs. 8.33 (7.75-9.15), p = 0.017, and 9.75 (8.35-10.50) vs. 8.33 (7.75-9.15), p = 0.002, respectively). There was no significant difference in CAVI values between the MUCH and SUCH groups. Multinomial logistic regression analysis exhibited that compared with the CH group, increased CAVI levels were positively associated with the presence of MUCH and SUCH (OR 2.046, 95% CI (1.239-3.381), p = 0.005; OR 2.215, 95% CI (1.310-3.747), p = 0.003) after adjusting for confounders. However, there was a similar trend of the CAVI in the MUCH and SUCH groups (OR 0.924, 95% CI (0.629-1.356), p = 0.686). In summary, our findings support, for the first time, the novel notion that CAVI as an arterial stiffness parameter is an independent risk factor for MUCH, being equally important to MUCH and SUCH. When the assessed CAVI is high in hypertensive patients with normotensive office BP levels, it is necessary to further investigate with a 24 h ambulatory BP monitoring to estimate the longstanding BP control. CAVI may be used as a noninvasive indicator to identify patients with MUCH earlier.Copyright © 2022 Ning Wang et al.