Objective The ratio of basal distal intracoronary pressure (Pd) and aortic pressure (Pa) is a nonhyperemic index for the severity of coronary artery stenosis. The aim of the current study was to evaluate the clinical usefulness of a hybrid baseline Pd/Pa-fractional flow reserve (FFR) strategy in reducing the need for hyperemia. Methods In this study, 570 lesions from 527 consecutive patients who had both baseline Pd/Pa and FFR determined were evaluated retrospectively. To evaluate the hybrid baseline Pd/Pa-FFR approach, patients were categorized into treatment, deferral, and undetermined groups on the basis of their baseline Pd/Pa. Thereafter, patients in the undetermined group were assigned to FFR-guided treatment or deferral on the basis of an FFR cutoff value of 0.80 or lower. Major adverse cardiac events were evaluated in a median of 48.8 months (interquartile range, 35.0-66.4). Results A hybrid strategy using a deferral baseline Pd/Pa value of 1.00 (negative predictive value of 100%) and a treatment baseline Pd/Pa value of 0.86 or lower (positive predictive value of 100%), and limiting adenosine to a baseline Pd/Pa value between 0.87 and 0.99 would prevent the need for vasodilator drugs in 14.6% of lesions (14.0% patients), maintaining 100% agreement with an FFR-only strategy. However, adenosine-free lesions are increased to 59.6%, with 91% agreement. There was no difference in the major adverse cardiac event-free survival rate at 5 years between baseline Pd/Pa-guided and FFR-guided treatment patients (70.8 vs. 76.3%, P = 0.63), or between baseline Pd/Pa-guided and FFR-guided deferral patients (71.3 vs. 82.4%, P = 0.99). Conclusion The current study reports a range of baseline Pd/Pa values that can predict myocardial ischemia without the need for inducing hyperemia. Adoption of this hybrid baseline Pd/Pa-FFR approach can reduce the need for drug-induced hyperemia. Coron Artery Dis 26:49-55 (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.