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Background While several randomized trials have shown conflicting results regarding the comparative effectiveness of on- and off-pump coronary arterial bypass grafting (CABG), research on long-term outcomes in large-scale, real-world clinical settings are limited. We sought to examine the comparative effectiveness of on- and off-pump CABG in a real-world clinical setting. Methods Using the nationwide claims database of the Korean National Health Insurance Service, we identified patients who underwent isolated CABG from 2004 to 2013. Propensity-score matching with multivariable adjustment was used to assemble a cohort of patients with similar baseline characteristics. Results Among 23,828 patients, 12,639 in the off-pump (53.0%) and 11,189 in the on-pump (47.0%) groups were enrolled. After matching, 6,483 pairs were included in the final analysis. At 30 days, there was no significant difference in adjusted mortality between the off- and on-pump groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.87-1.16). During long-term follow-up (100% complete; median 5.3yrs, maximum 13.2yrs), however, off-pump CABG was associated with a higher risk of mortality than on-pump CABG (HR, 1.09; 95% CI, 1.03-1.15). The risks of myocardial infarction (MI) (HR, 1.3; 95% CI, 1.16-1.45) and repeat revascularization (HR, 1.50; 95% CI, 1.37-1.63) were also significantly higher in the off-pump CABG group than in the on-pump CABG group, while the stroke risk was similar inter-groups (HR, 0.99; 95% CI, 0.87-1.13). Conclusions In this contemporary, nationwide, clinical practice claim registry, off-pump CABG was associated with higher long-term risks of mortality, MI, and repeat revascularization than on-pump CABG.