Background Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between diff erent modes of DAPT cessation and cardiovascular risk after PCI. Methods The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecifi ed categories for DAPT cessation included physicianrecommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the eff ect of DAPT cessation on major adverse events (MACE [composite of cardiac death, defi nite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the fi rst event. This study is registered with ClinicalTrials.gov, number NCT00998127. Findings We enrolled 5031 patients undergoing PCI, including 5018 in the fi nal study population. Over 2 years, the overall incidence of any DAPT cessation was 57•3%. Rate of any discontinuation was 40•8%, of interruption was 10•5%, and of disruption was 14•4%. The corresponding overall 2 year MACE rate was 11•5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1•41 (95% CI 0•94-2•12; p=0•10) and to disruption was 1•50 (1•14-1.97; p=0•004). Within 7 days, 8-30 days, and more than 30 days after disruption, adjusted HRs were 7•04 (3•31-14•95), 2•17 (0•97-4•88), and 1•3 (0•97-1•76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0•63 [0•46- 0•86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE defi nition that did not include target lesion revascularisation. Interpretation In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type.