Objective: There is a gap in the literature regarding the association between stiffness and myocardial ischemia. Arterial stiffness (AS) is an independent risk factor for cardiovascular disease, directly related to coronary atherosclerosis, an entity with an unfavorable cardiovascular prognosis frequently encountered in patients with hypertension. The aim of this study was to investigate the relationship between AS and Coronary Microvascular Dysfunction (MVD). Design and method: We examined 23 hypertensive patients [10 female, 43%, mean age: 61.5±10.1 years, mean office blood pressure (BP): 147/88±10/9 mmHg] and 28 MVD patients (19 female, 68%, mean age: 58.3±4.6 years, average office BP: 139/81±16/13 mmHg). In the group of patients with angina, MVD was defined by a standardized systematic protocol in which coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. MVD patients were classified into 2 groups, structural and functional endotype, based on commonly used cut-offs (impaired CFR < 2.5, increased IMR > 25). In addition, in all participants, arterial stiffness was assessed using the aortic augmentation index (AIx), derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the radial artery. Results: In the MVD group, the coronary flow reserve (CFR) was 1.4±0.9 and the index of microvascular resistance (IMR) was 43.9±30 IU. Of the 28 patients with impaired CFR, 8 (28%) had normal IMR consistent with functional CMD endotype, and 20 (71%) had abnormal IMR associated with structural alterations of the microvasculature. AIx was found to be increased in MVD patients compared to hypertensives (35.4±10.8 vs 27.4±12.6%, p = 0.031). This difference in AIx between the CMD and asymptomatic hypertensive controls was found to be statistically significant after adjustment for gender and age (p<0.05). No statistically significant difference was found in body mass index, renal function, history of dyslipidemia, diabetes mellitus, and smoking between groups. Conclusions: Arterial stiffness was found to be increased in patients with MVD compared to asymptomatic hypertensive individuals. These results suggest that therapies targeting vascular stiffening could provide additional clinical benefit in patients with impaired coronary microvasculature.