Experience with intravascular ultrasound (IVUS) and physiological methods for measuring coronary flow reserve during percutaneous coronary interventions (PCI) has shown that quantitative coronary angiography (QCA) is far from ideal to evaluate immediate efficacy of PCI. Balloon angioplasty under IVUS guidance allows for safe use of larger balloon catheters than estimated by QCA and provides long-term outcomes similar to stenting. The aim of the present study was to evaluate the effect of percutaneous balloon angioplasty guided by IVUS on postprocedural coronary flow reserve. The study population included 21 patients undergoing percutaneous transluminal coronary angioplasty using balloon catheters sized according to the angiographic reference segment diameter, in whom residual stenosis did not exceed 35% and there was no vascular wall dissection requiring stenting. CFR was measured at baseline, after dilatation with QCA sized balloons and after IVUS guided intervention. As compared with angio-graphically guided balloon angio-plasty, PTCA with IVUS guidance resulted in a significantly increased CFR relative to its baseline value. The present findings suggest that impaired coronary flow reserve after angiographically guided PCI may be a result of non-optimal vessel dilatation due to limitations of quantitative coronary angiography in balloon sizing. PCI with IVUS guidance allows for improvement of CFR as compared with conventional balloon angioplasty.