A follow-up study including 2,203 patients from a US-based randomized trial shows that CABG surgery performed without cardiopulmonary bypass (off pump) is associated with lower rates of 5-year survival and event-free survival than CABG surgery with cardiopulmonary bypass (on pump). In all 5-year clinical outcomes evaluated, off-pump CABG surgery did not confer any advantage over on-pump CABG surgery: the rate of the primary outcome of death from any cause was higher with the off-pump approach than with the on-pump procedure (15.2% versus 11.9%; relative risk 1.28, 95% CI 1.03–1.58, P = 0.02), as was the rate of the primary outcome of major adverse cardiovascular events (31.0% versus 27.1%; relative risk 1.14, 95% CI 1.00–1.30, P = 0.046). No between-group differences were found for the 5-year secondary outcomes of nonfatal myocardial infarction, death from cardiac causes, repeat revascularization, and repeat CABG surgery.