Few studies have documented changes in global absolute coronary blood flow and global coronary flow reserve after percutaneous coronary intervention (PCI) in relation to regional physiological measures. Phase-contrast cine-magnetic resonance of the coronary sinus is a promising approach to quantify global absolute coronary blood flow. We aimed to assess the impact of elective PCI on global absolute coronary blood flow and global coronary flow reserve by quantifying coronary sinus flow (CSF) using phase-contrast cine-magnetic resonance in relation to regional physiological indices. We prospectively studied 54 patients with stable angina undergoing elective PCI for a single proximal lesion. Phase-contrast cine-magnetic resonance was used to assess CSF and CSF reserve at rest and during maximum hyperemia, before and after PCI. Regional physiological indices were obtained during PCI. A complete data set was obtained in 50 patients. Hyperemic CSF increased significantly after PCI (pre-PCI, 230.2 [167.4-282.8] mL/min; post-PCI, 267.4 [224.1-346.2] mL/min; P<0.01), although 12 patients (24.0%) showed a decrease, despite successful PCI and improved fractional flow reserve. CSF reserve numerically, albeit not statistically significant (P=0.19), increased from 2.65 (1.95-3.96) to 2.98 (2.13-4.32). Patients with decreased CSF after PCI were associated with significantly greater pre-PCI hyperemic CSF, lower global coronary vascular resistance, lower regional microcirculatory resistance, and higher fractional flow reserve (all P<0.01). Fractional flow reserve-guided PCI in patients with single de novo lesions was associated with increased absolute hyperemic CSF, although 24% of patients showed decreased hyperemic CSF, despite successful and uncomplicated PCI. The present approach combining regional and global physiological assessments may provide a novel insight into the dynamic behavior of the coronary hemodynamics and microvascular function after PCI.