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PCI has revolutionized the treatment of CAD, reducing mortality and improving recovery. At the same time, AF increases the risk of stroke, thus requiring anticoagulation. The combination of antiplatelet and anticoagulant therapies in patients undergoing PCI is challenging because of increased bleeding risks. This literature review explores the controversies surrounding dual antithrombotic therapy (DAT) and triple antithrombotic therapy (TAT), evaluating their efficacy and safety in mitigating thrombotic and hemorrhagic risks. Key clinical trials and guidelines advocate the use of DAT, especially in patients at high bleeding risk, underlining its role in reducing complications without compromising ischemic protection. Furthermore, advances in stent technologies, personalized medicine tools, and pharmacogenomics have further refined treatment strategies toward tailored approaches. Despite these developments, the optimal duration of therapy remains debated, as do patient selection and the need to balance ischemic and bleeding risks, particularly in complex patients.This review underscores the need for an individualized, evidence-based approach to optimize outcomes and inform future guidelines in managing this high-risk population. Emerging therapies and real-world evidence\u2014such as trials investigating Factor XI inhibitors and bioresorbable scaffolds\u2014are promising, aiming to reduce bleeding risk and improve long-term outcomes in patients with CAD and AF. 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