The aim of this study was to elucidate if patients with coronary artery disease (CAD), who fail to respond to revascularization procedures, can improve from individual shear rate therapy (ISRT). The ISRT is an adaptation of the external counterpulsation with lower individual treatment pressures based on Doppler-ultrasound measurements during counterpulsation. In contrast to the external counterpulsation therapy, the ISRT is based on the detection of the individual intra-arterial shear rate. Here we report about the first clinical trial of 31 patients with CAD who were enrolled for 30 sessions of ISRT. To determine the therapeutic effect of ISRT we measured the exercise capacity, the arterial stiffness, the aortic wave reflection, and the 24-hour blood pressure before and after 30 treatment sessions. After 6 weeks of accomplished ISRT the walking distance during the 6-minute walking test extended by 78 m (p = 0.007). The total exercise duration in the exercise stress electrocardiogram increased by 84 seconds (p = 0.012) but not the stress intensity (p = 0.086). The pulse wave velocity decreased by 1.2 m/s (p = 0.004) and demonstrated a decrease in arterial stiffness. Pulse wave analysis results demonstrated a progressive decrease in central blood pressure by 12 mmHg (p = 0.008), in pulse pressure by 9 mmHg (p = 0.005), and in augmentation pressure by 5.3 mmHg (p = 0.004). The 24-hour blood pressure decreased systolic by 15 mmHg (p <0.001) and diastolic by 8 mmHg (p = 0.033). The patients also benefited subjectively followed by New York Heart Association and Canadian Cardiovascular Society classifications. In conclusion, the ISRT is an effective treatment for patients with CAD to improve cardiac fitness, arterial stiffness, and to reduce blood pressure.