Patients with microvascular angina (MVA) often have persistence of symptoms despite full classical anti-ischemic therapy. In this study, we assessed the effect of ivabradine and ranolazine in MVA patients. We randomized 46 patients with stable MVA (effort angina, positive exercise stress test EST, normal coronary angiography, coronary flow reserve <2.5), who had symptoms inadequately controlled by standard anti-ischemic therapy, to ivabradine (5 mg twice daily), ranolazine (375 mg twice daily), or placebo for 4 weeks. The Seattle Angina Questionnaire (SAQ), EuroQoL scale, and EST were assessed at baseline and after treatment. Coronary microvascular dilation in response to adenosine and to cold pressor test and peripheral endothelial function (by flow-mediated dilation) were also assessed. Both drugs improved SAQ items and EuroQoL scale compared with placebo (p <0.01 for all), with ranolazine showing some more significant effects compared with ivabradine, on some SAQ items and EuroQoL scale (p <0.05). Time to 1-mm ST-segment depression and EST duration were improved by ranolazine compared with placebo. No effects on coronary microvascular function and on flow-mediated dilation were observed with drugs or placebo. In conclusion, ranolazine and ivabradine may have a therapeutic role in MVA patients with inadequate control of symptoms in combination with usual anti-ischemic therapy.