The optimal approach to percutaneous coronary intervention (PCI) of bifurcation lesions remains unclear, reflecting lack of long-term follow-up and heterogeneity of lesions encountered. We evaluated the long-term outcome of patients undergoing bifurcation PCI followed in the prospective bifurcation registry at the University Health Network, Toronto, Ontario, Canada. Of 526 patients undergoing bifurcation PCI between November 2003 and March 2005, most (n = 406) were treated by main vessel stenting only (n = 266) or crush/culotte stenting (n = 140). After median follow-up of 26.5 months, major adverse cardiac events (MACEs) and Canadian Cardiovascular Society class > or =2 angina occurred in 28.5% and 22.3% of patients in these groups, respectively (p = 0.190), whereas MACE rates were 20.8% for main vessel stenting and 18.7% for crush/culotte stenting (p = 0.670). A low bifurcation angle was associated with better outcomes in the crush/culotte group but had no effect on outcome of patients treated with main vessel stenting only. Use of crush/culotte techniques independently predicted freedom from MACEs or Canadian Cardiovascular Society class > or =2 angina compared with main vessel stenting only (odds ratio 0.55, 95% confidence interval 0.32 to 0.94, p = 0.029). In conclusion, the use of crush/culotte stenting is safe, with efficacy and MACE rates being similar to main vessel stenting alone. Our observations regarding the effect of lesion characteristics such as bifurcation angle and extent of side branch disease on outcome underscore the need for randomized trials that are inclusive of patients with complex side branch disease.