Complex percutaneous coronary intervention (PCI) represents a growing proportion of contemporary coronary revascularization, driven by aging populations, increasing comorbidity burden, and advances in interventional techniques. Complex PCI encompasses a spectrum of anatomically and procedurally challenging lesions, including left main disease, bifurcation lesions requiring two-stent strategies, chronic total occlusions, long stent lengths, severe calcification requiring atherectomy, and multivessel revascularization. Antithrombotic therapy, comprising antiplatelet and anticoagulant agents, is essential for preventing stent thrombosis and other ischemic events in both the early and long-term phases after PCI. While antithrombotic therapy mitigates ischemic risks associated with complex PCI, these patients frequently carry high-bleeding risk, thus making the choice of antithrombotic regimen challenging. Recent guideline recommendations emphasize balancing ischemic and bleeding risks rather than relying solely on procedural complexity. This review synthesizes contemporary evidence, guideline recommendations, and clinical considerations for antithrombotic therapy after complex PCI.