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Aims: In 2010, the European Society of Cardiology Guidelines on atrial fibrillation (AF) introduced the CHA2DS2‐VASc score to guide initiation of oral anticoagulation. In patients with AF undergoing percutaneous coronary intervention (PCI), triple therapy with oral anticoagulation and dual antiplatelet therapy was recommended to reduce ischaemic risk. We examined how the CHA2DS2‐VASc score impacted oral anticoagulation use and risks of ischaemic and hospitalized bleeding events in patients with AF undergoing PCI. Methods: We included 6,014 patients with AF undergoing first‐time PCI in Western Denmark between 2003 and 2017. We divided patients into four groups based on year of PCI and estimated 1‐year risks of major adverse cardiac events (MACE) and hospitalization for bleeding. Results: The proportion of oral anticoagulation users was 48% in 2003–2006 and 49% in 2006–2010. Following the CHA2DS2‐VASc score implementation, the proportion increased to 59% in 2011–2014 and 77% in 2015–2017. Using 2003–2006 as reference, risks of MACE were similar in 2007–2010 (adjusted relative risk [RRadj] 0.99, 95% confidence interval [CI] 0.83–1.18) and 2011–2014 (RRadj 0.92, 95% CI 0.78–1.09), but declined by 23% in 2015–2017 (RRadj 0.77, 95% CI 0.65–0.92). Hospitalizations for bleeding did not increase despite wider use of triple therapy. Conclusion: Implementation of the CHA2DS2‐VASc score in the 2010 European guidelines on AF was associated with an increased utilization of oral anticoagulation and triple therapy among AF patients undergoing PCI. These changes were associated with a gradual decline in the risk of MACE, while the risk of hospitalized bleeding remained unchanged. [ABSTRACT FROM AUTHOR]