This study gains insight on the nature of flow blockage effects of small guidewire catheter sensors in measuring mean trans‐stenotic pressure gradients $\Delta\tilde{p}$ across significant coronary artery stenoses. Detailed pulsatile hemodynamic computations were made in conjunction with previously reported clinical data in a group of patients with clinically significant coronary lesions before angioplasty. Results of this study ascertain changes in hemodynamic conditions due to the insertion of a guidewire catheter (d_i=0.46 mm) across the lesions used to directly determine the mean pressure gradient $(\Delta\tilde{p})$ and fall in distal mean coronary pressure ( $\tilde{p}_{r})$ . For the 32 patient group of Wilson et al. [1988] (minimal lesion diameter d_m=0.95 mm; 90% mean area stenosis; proximal measured coronary flow reserve (CFR) of 2.3 in the abnormal range) the diameter ratio of guidewire catheter to minimal lesion was 0.48, causing a tighter “artifactual” mean area stenosis of 92.1%. The results of the computations indicated a significant shift in the $\Delta\tilde{p}$ – $\widetilde{Q}$ relation due to guidewire induced increases in flow resistances ( $\widetilde{R}=\Delta\tilde{p}/\widetilde{Q})$ of 110% for hyperemic flow, a 35% blockage in hyperemic flow $(\widetilde{Q}_{h})$ and a phase shift of the coronary flow waveform to systolic predominance. These alterations in flow resulted in a fall in distal mean coronary pressure (at lower mean flow rates) below the patho‐physiological range of $\tilde{p}_{rh}\sim 55$ mmHg, which is known to cause ischemia in the subendocardium (Brown et al. [1984]) and coincides with symptomatic angina. Transient wall shear stress levels in the narrow throat region (with flow blockage) were of the order of levels during hyperemic conditions for patho‐physiological flow. In the separated flow region along the distal vessel wall, vortical flow cells formed periodically during the systolic phase when instantaneous Reynolds numbers Re_e(t) exceeded about 110. For patho‐physiological flow without the presence of the guidewire these vortical flow cells were much stronger than in the more viscous flow regime with the guidewire present. The non‐dimensional pressure data given in tabular form may be useful in interpretation of guidewire measurements done clinically for lesions of similar geometry and severity.