BACKGROUND: Overlapping first generation sirolimus- and paclitaxel-eluting stents are associated with persistent inflammation, fibrin deposition and delayed endothelialisation in preclinical models, and adverse angiographic and clinical outcomes--including death and myocardial infarction (MI)--in clinical studies. OBJECTIVES: To establish as to whether there are any safety concerns with newer generation drug-eluting stents (DES). DESIGN: Propensity score adjustment of baseline anatomical and clinical characteristics were used to compare clinical outcomes (Kaplan-Meier estimates) between patients implanted with overlapping DES (Resolute zotarolimus-eluting stent (R-ZES) or R-ZES/other DES) against no overlapping DES. Additionally, angiographic outcomes for overlapping R-ZES and everolimus-eluting stents were evaluated in the randomised RESOLUTE All-Comers Trial. SETTING: Patient level data from five controlled studies of the RESOLUTE Global Clinical Program evaluating the R-ZES were pooled. Enrollment criteria were generally unrestrictive. PATIENTS: 5130 patients. MAIN OUTCOME MEASURES: 2-year clinical outcomes and 13-month angiographic outcomes. RESULTS: 644 of 5130 patients (12.6 ) in the RESOLUTE Global Clinical Program underwent overlapping DES implantation. Implantation of overlapping DES was associated with an increased frequency of MI and more complex/calcified lesion types at baseline. Adjusted in-hospital, 30-day and 2-year clinical outcomes indicated comparable cardiac death (2-year overlap vs non-overlap: 3.0 vs 2.1 , p=0.36), major adverse cardiac events (13.3 vs 10.7 , p=0.19), target-vessel MI (3.9 vs 3.4 , p=0.40), clinically driven target vessel revascularisation (7.7 vs 6.5 , p=0.32), and definite/probable stent thrombosis (1.4 vs 0.9 , p=0.28). 13-month adjusted angiographic outcomes were comparable between overlapping and non-overlapping DES. CONCLUSIONS: Overlapping newer generation DES are safe and effective, with comparable angiographic and clinical outcomes--including repeat revascularisation--to non-overlapping DES.