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The difference in the usefulness of routine angiographic follow-up (RAF) and clinical follow-up (CF) after a percutaneous coronary intervention (PCI) in multivessel coronary artery disease (MVD) patients has not been well clarified as yet.A total of 642 consecutive MVD patients who underwent PCI with drug-eluting stents (DES) were enrolled. RAF was performed at 6–9 months after the index PCI (n=374) and others were medically managed and clinically followed (n=268). Patients who experienced clinical events including death, myocardial infarction (MI), and ischemia-driven PCI before 1 year were excluded. To adjust for any potential confounders, a propensity scorematched analysis was carried out using the logistic regression model and two propensity-matched groups (193 pairs, n=386, C-statistic=0.744) were generated. Cumulative clinical outcomes up to 3 years were compared between the RAF group and the CF group.During the 3-year follow-up period, the cumulative incidence of revascularization [target lesion revascularization: odds ratio (OR), 4.21; 95% confidence interval (CI), 1.67–10.6; P=0.001) and target vessel revascularization (TVR: OR, 4.69; 95% CI, 2.00–11.0; P<0.001, target vessel revascularization: OR, 4.69; 95% CI, 2.00–1011.0; P<0.001] and major adverse cardiovascular events (composite of death, repeat PCI and MI: OR, 2.96; 95% CI, 1.62–105.42, P<0.001) were significantly higher in the RAF group compared with the CF group. However, the 3-year incidence of death (OR, 1.41; 95% CI, 0.44–104.53; P=0.558) or MI (OR, 2.58; 95% CI, 0.79–108.37; P=0.102) was not different between the two groups. In MVD patients treated with second-generation DESs, the incidence of repeat revascularization (target lesion revascularization and target vessel revascularization) was not different between the two groups.Conclusion RAF following index PCI with DES in multivessel CAD patients was associated with increased incidence of revascularization and major adverse cardiovascular events. However, in MVD patients treated with second-generation DESs, repeat revascularization incidence was similar between two different follow-up strategies up to 3 years.