Percutaneous coronary intervention of bifurcation lesions is known to be associated with higher risk of complications than non-bifurcation lesions. In the drug-eluting stent (DES) era, the risk of stent thrombosis (ST) is of particular concern because of its catastrophic consequences and late occurrence. The risk of ST in PCI of bifurcation lesions remains low even with the use of a two-stent strategy compared with a provisional side branch stenting strategy. Also, the use of DES has no higher risk of ST compared with bare metal stents. Prevention of ST in PCI of bifurcation lesions remains pivotal and must include appropriate duration of dual antiplatelet therapy, meticulous attention to stent deployment techniques, and use of intravascular ultrasound for guidance whenever needed.