Background: Hypertension clinical treatment largely relies on different drugs. Some of these drugs are thought to exhibit specific protective functions in addition to those resulting from blood pressure reduction per se. Through a validated multiscale mathematical model of the cardiovascular system, we studied the impact of commonly-used antihypertensive drugs on myocardial oxygen supply–consumption balance, which plays a crucial role in type 2 myocardial infarction. Methods: Forty-two wash-out hypertensive patients were included in this study. Patients’ demographics, heart rate, brachial pressure, Left Ventricular (LV) volumes and carotid-femoral pulse wave velocity were used to set to patient specific condition a largely accepted benchmark data set describing generic healthy subjects. Starting from literature data, drugs effects were modeled by means of six coefficients, describing LV function, heart rate, peripheral resistances and arterial stiffness. These drug-specific sextuplets were used to multiply some parameters of each patient model to simulate drugs impact. Results: Our results ascribed the well-known major cardioprotective efficiency of β blockers to a positive change of myocardial oxygen balance. This was due to the concomitant reduction in LV work and increase in coronary flow. Similarly, RAAS blockers induced several positive changes, but to a reduced extent. In contrast, calcium channel blockers seem to induce some potentially negative effects on myocardial oxygen balance. Conclusions: Patient specific multiscale mathematical model is able to reproduce clinically-relevant changes in coronary hemodynamics and ventricular function driven by anti-hypertensive drugs. Further studies are needed to evaluate eventual clinical usefulness of in-silico modeling of anti-hypertensive drugs.