Resistant hypertension is associated with increased risk for cardiovascular events. Coronary flow reserve (CFR) is impaired in patients with hypertension and an independent predictor of cardiac mortality. However, there are no published data on CFR in the subset of treatment-resistant hypertension. The aim of this study was to assess CFR in patients with resistant hypertension. Twenty-five consecutive patients with primary resistant hypertension, scheduled for renal denervation, 25 matched patients with controlled hypertension, and 25 healthy controls underwent transthoracic colour Doppler echocardiography at rest and during adenosine infusion. Patients with hypertension were pair-matched with regard to age, sex, ischemic heart disease, diabetes mellitus, smoking status, and body-mass index. Healthy controls were selected according to age and sex. Mean flow velocity was measured in the left coronary anterior descending artery. Baseline mean flow velocities were similar in patients with controlled and resistant hypertension. CFR was significantly lower in patients with resistant hypertension as compared to individuals with non-resistant hypertension (2.7 ± 0.6 vs. 3.1 ± 0.8; p = 0.03). Systolic office blood pressure was significantly higher in patients with resistant hypertension (169 ± 20 vs. 144 ± 21 mm Hg; p < 0.01). Heart rate, ventricular mass, and ejection fraction were similar in the two groups. Healthy controls showed significantly lower baseline velocity, higher CFR, and lower blood pressure as compared to hypertensives. Resistant hypertension was associated with impaired CFR as compared to individuals with non-resistant hypertension indicating impaired cardiac microvascular function which may contribute to the increased risk of adverse outcome in patients with resistant hypertension.