Background: This study evaluated outcomes of cardiac operations with very prolonged cardiopulmonary bypass (CPB) times. Methods: This was a retrospective study of cardiac surgical procedures with very-long CBP times (≥300 minutes) performed at a single institution. Primary outcomes of operative (≤30-day) and one-year mortality were evaluated, and secondary outcomes included use of mechanical support and postoperative complications. A probability analysis was also conducted to identify the correlation between operative mortality and CPB time. Results: 293 patients were included with a Society of Thoracic Surgeons predicted risk of mortality of 2.51% (IQR 1.32%- 4.70%), and median CPB time of 340 minutes (IQR 315.0-385.0). Preoperative mechanical support included intra-aortic balloon pump (IABP, n=4, 1.4%), Impella (n=0), or extracorporeal membrane oxygenation (ECMO, n=2, 0.7%). Intraoperative and operative mortality were 5.1% and 22.5%, respectively. Intraoperative or postoperative mechanical support were utilized in 90 (30.7%) cases, including IABP (n=65, 22.2%), Impella (n=2, 0.68%), or ECMO (n=23, 7.8%). Postoperative complications included prolonged mechanical ventilation (n=121, 41.3%), renal failure (n=71, 24.2%), stroke (n=20, 6.8%), and reoperation (n=95, 32.4%). One-year survival for the overall cohort was 61.4%. Probability analysis identified a CPB time of 446 minutes to be associated with 50% odds of operative mortality. Conclusions: Cardiac operations requiring very-long CPB times are associated with high rates of operative mortality and morbidity, with a 50% operative mortality rate predicted for those with a CPB time of 446 minutes or longer. Nonetheless, the majority of patients survive at least 1 year, and these cases should not be considered futile.