Complex percutaneous coronary intervention (PCI) requires careful anticoagulation to prevent thrombotic complications while minimizing bleeding risk. Patients undergoing left main PCI, bifurcation stenting, chronic total occlusion intervention, atherectomy-assisted PCI, multivessel PCI, and long-stent procedures often have prolonged procedural time, increased device manipulation, higher thrombus risk, and greater bleeding vulnerability. This article reviews contemporary anticoagulation strategies during complex PCI, including unfractionated heparin, bivalirudin, glycoprotein IIb/IIIa inhibitors, anticoagulation monitoring, reversal considerations, and management of high-risk patient groups.