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Background: Studies have suggested that use of prolonged dual antiplatelet therapy (DAPT) following new generation drug-eluting stent implantation may increase costs and potential bleeding events.This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization) at 2-year follow-up.Methods: The SEEDS study is a prospective, multicenter study, where patients (n =1900) with small vessel, long lesion, or multi-vessel diseases underwent EES implantation.Detailed DAPT status was collected at baseline, 6-month, 1-and 2-year.DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days.The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and major bleeding (Bleeding Academic Research Consortium Ⅱ-Ⅴ)) were investigated according to the DAPT status at 2-year follow-up.Results: DAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years.It was observed that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST (0.7%).DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096-4.980, P =0.715) and NACE (HR: 1.041, 95% CI: 0.145-7.454, P =0.968).Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1-and 2-year (1.4%).There was a high frequency of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT treatment.Conclusions: Prolonged DAPT use was not associated with improved clinical safety.The study emphasized that duration of DAPT needs to be shortened in Chinese patients following EES implantation (ClinicalTrials.gov identifier: NCT 01157455).