Background: Coronary stents are commonly used in percutaneous coronary interventions (PCI). Bare-metal stents (BMS) as the first generation stent and paclitaxel-eluting stents (PES) as a second generation stent are widely deployed in PCIs. However, the long-term comparative effectiveness of BMS vs PES in the real practice remains unclear. Our aim was to assess a comprehensive set of 6-year clinical outcomes of all patients undergoing PCI with either BMS or PES placement and to determine comparative effectiveness of BMS vs PES in “off-label” (ST Segment Elevation Myocardial , totally occluded lesions, left main disease, multiple vessels diseased, bypassed graft lesions, and ejection fraction75 years, and diabetes) patient subgroups. Methods: A 6-year longitudinal database was created by linking data from the New York State (NYS) PCI registry, the NYS Cardiac Surgery Reporting System (CSRS) registry, the Statewide Planning and Research Cooperative System (SPARCS), the National Death Index (NDI) file, and the U.S. Census data (2010) for patients undergoing PCI with BMS or PES placement from January 1, 2006 through December 31, 2007. Outcomes included all-cause mortality, acute myocardial infarction (AMI), subsequent coronary revascularizations (PCI or coronary artery bypass graft surgery) and target-vessel PCI (TVPCI). Propensity score-matched patients undergoing BMS or PES (n=13,879 pairs) were compared with respect to 6-year outcomes using Kaplan-Meier estimates and Cox proportional hazards regression models applied to propensity-matched patients. Results: There were no significant differences in demographics, comorbidities, clinical profile, vessel/lesion related risk factors, and hospital/physician level characteristics between BMS and PES after propensity score matching. Kaplan-Meier estimates indicated that there were significant differences between BMS and PES for 6-year all-cause mortality (BMS: 26.87%, PES: 22.0%, Log-rank P<0.001), AMI (BMS: 8.91%, PES: 8.89%, P=0.045), repeat revascularization (BMS: 34.14%, PES: 36.27%, P=0.004), and TVPCI (BMS: 15.43%, PES: 15.28%, P=0.01). After further adjustment with Cox models, PES use was associated with significantly lower occurrence of 6-year all-cause mortality (adjusted hazard ratio : 0.74, P<0.001), AMI (AHR: 0.91, P=0.04), and TVPCI (AHR: 0.92, P=0.02) but higher occurrence of 6-year repeat revascularization (AHR: 1.08, P=0.001). The reason why BMS had lower repeat revascularization rate was because of its lower rate of repeat PCI in non-target vessels. For “off-label” and “high-risk” subgroups, PES had superior or non-inferior outcomes relative to BMS. Conclusion: Overall, PES improved clinical outcomes compared to BMS at 6 years. For each “off-label” or “high-risk” subgroup, the comparative effectiveness of PES vs BMS varied by the outcome assessed.