Background Coronary artery disease (CAD) patterns play an essential role in the decision-making process about revascularization. The pullback pressure gradient (PPG) quantifies CAD patterns as either focal or diffuse based on fractional flow reserve (FFR) pullbacks. The objective of this study was to evaluate the impact of CAD patterns on acute percutaneous coronary intervention (PCI) results considered surrogates of clinical outcomes. Methods and Results This was a prospective, multicenter study of patients with hemodynamically significant CAD undergoing PCI. Motorized FFR pullbacks and optical coherence tomography (OCT) were performed before and after PCI. Post-PCI FFR >0.90 was considered an optimal result. Focal disease was defined as PPG >0.73 (highest PPG tertile). Overall, 113 patients (116 vessels) were included. Patients with focal disease were younger than those with diffuse CAD (61.4±9.9 versus 65.1±8.7 years, P=0.042). PCI in vessels with high PPG (focal CAD) resulted in higher post-PCI FFR (0.91±0.07 in the focal group versus 0.86±0.05 in the diffuse group, P<0.001) and larger minimal stent area (6.3±2.3 mm ² in focal versus 5.3±1.8 mm ² in diffuse CAD, P=0.015) compared withvessels with low PPG (diffuse CAD). The PPG was associated with the change in FFR after PCI (R ² =0.51, P<0.001). The PPG significantly improved the capacity to predict optimal PCI results compared with an angiographic assessment of CAD patterns (area under the curve _PPG 0.81 [95% CI, 0.73-0.88] versus area under the curve _angio 0.51 [95% CI, 0.42-0.60]; P<0.001). Conclusions PCI in vessels with focal disease defined by the PPG resulted in greater improvement in epicardial conductance and larger minimal stent area compared with diffuse disease. PPG, but not angiographically defined CAD patterns, distinguished patients attaining superior procedural outcomes. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03782688.