OBJECTIVES: To investigate the until now undefined extent of differences in baseline characteristics, practice patterns and clinical outcomes of patients undergoing coronary artery bypass grafting (CABG) for complex coronary artery disease in the USA versus Europe. METHODS: The impact of geographic enrolment on clinical outcomes was explored using the as-treated population of 1510 patients with de novo left main and/or three-vessel disease who underwent CABG in either the SYNTAX randomized trial or registries, and who were followed up for 5 years. RESULTS: There were 259 (17%) patients enrolled in the USA. Patients in the USA had more comorbidities. Off-pump procedures were more frequent in the USA (32 vs 13% in Europe; P < 0.001), and crystalloid cardioplegia was used less often (17 vs 38% in Europe; P < 0.001). In the USA, more grafts per patient were used (3.1 +/- 0.8 vs 2.7 +/- 0.7 in Europe; P < 0.001), with less complete arterial grafting (5 vs 18% in Europe; P < 0.001) but more complete revascularization (80 vs 66% in Europe; P < 0.001). At 5-year follow-up, patients treated in the USA versus Europe had comparable rates of major adverse cardiac and cerebrovascular events (MACCEs: 28.7 vs 24.3%, respectively; P = 0.11) and the composite safety endpoint of death, stroke and myocardial infarction (MI; 15.3 vs 17.5%, respectively; P = 0.43), but a significantly higher rate of repeat revascularization (15.0 vs 9.8%, respectively; P = 0.011) driven by repeat percutaneous coronary intervention (14.6 vs 9.2%; P = 0.005) and not repeat CABG (0.4 vs 0.8%; P = 0.48). Rates of graft occlusion were significantly higher in the USA versus Europe (8.7 vs 3.2%; P < 0.001). In multivariate analysis, enrolment in the USA was a non-significant predictor of MACCE [hazard ratio (HR) = 1.31, 95% confidence interval (95% CI) 1.00-1.73; P = 0.053], but independently predicted repeat revascularization (HR = 1.66, 95% CI 1.12-2.46; P = 0.011) and graft occlusion (HR = 2.65, 95% CI 1.52-4.62; P = 0.001). It was also a non-significant predictor of reduced rates of MI (HR = 0.38, 95% CI 0.14-1.06; P = 0.064). Differences between the USA and Europe were most pronounced among patients who underwent off-pump CABG. CONCLUSIONS: Repeat revascularization rates following CABG in the USA versus Europe were increased at 5 years, particularly in off-pump patients. There was no significant difference in the rate of death, stroke and MI.