The optimal revascularization strategy, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), for patients with multivessel coronary artery disease (MVD) remains controversial. The aim of the present study was to compare the long-term outcomes after selective PCI of only hemodynamically significant lesions (fractional flow reserve, or FFR < 0.75) to CABG of all stenoses in patients with MVD. In 150 patients with MVD referred for CABG, FFR was determined in 381 coronary arteries considered for bypass grafting. If the FFR was less than 0.75 in three vessels or in two vessels including the proximal left anterior descending (LAD) artery, CABG was performed (CABG group). If only one or two vessels were physiologically significant (not including the proximal LAD), PCI of those lesions was performed (PCI group). Of the 150 patients, 87 fulfilled the criteria for CABG and 63 for PCI. There were no significant differences in the angiographic or other baseline characteristics between the two groups. At 2-year follow-up, no differences were seen in adverse events, including repeat revascularization (event-free survival 74% in the CABG group and 72% in the PCI group). A similar number of patients were free from angina (84% in the CABG group and 82% in the PCI group). Importantly, the results in both groups were as good as the surgical groups in previous studies comparing PCI and CABG in MVD. In patients with multivessel disease, PCI in those with one or two hemodynamically significant lesions as identified by an FFR < 0.75 yields a similar favorable outcome as CABG in those with three or more culprit lesions despite a similar angiographic extent of disease.