The effect of alpha₁-receptor blockade with urapidil on coronary blood flow and left ventricular function has been attributed to relief of diffuse coronary vasoconstriction following percutaneous coronary intervention (PCI). We hypothesized that an increase in diastolic time fraction (DTF) contributes to this beneficial action of urapidil. In eleven patients with a 63% (SD 13) diameter stenosis, ECG, aortic pressure (P_a), and distal intracoronary pressure (P_d), and blood flow velocity were recorded at baseline and throughout adenosine-induced hyperemia. Measurements were obtained before and after PCI, and after subsequent alpha₁-receptor blockade with urapidil (10 mg ic). DTF was determined from the ECG and the aortic pressure waveform. Functional parameters such as coronary flow velocity reserve, fractional flow reserve, and an index of hyperemic microvascular resistance (HMR) were assessed. Urapidil administration after PCI induced an upward shift in the DTF-heart rate relationship, resulting in a 3.1% (SD 2.7) increase in hyperemic DTF at a constant heart rate (P<0.005) due to a shorter duration of systole. Hyperemic P_a and P_d decreased, respectively, by 6.1% (SD 6.6) (P<0.05) and 5.7% (SD 5.8) (P<0.01) after alpha₁-blockade. While epicardially measured functional parameters were on average not altered by alpha₁-blockade due to concurrent changes in pressure and heart rate, HMR decreased by urapidil in those patients where coronary pressure remained constant. In conclusion, alpha₁-receptor blockade after PCI produced a modest, but significant prolongation of DTF at a given heart rate, thereby providing an adjunctive beneficial mechanism for improving subendocardial perfusion, which critically depends on DTF.