The aim of this study was to investigate how a continuous quality improvement (CQI) program affected major morbidity and postoperative outcomes after cardiac surgery. Patients were divided into 2 groups: those who underwent surgery (coronary artery bypass grafting, isolated valve surgery, or coronary artery bypass grafting and valve surgery) after the establishment of a CQI program (from January 2005 to December 2006, n = 922) and those who underwent surgery beforehand (from January 2002 to December 2003, n = 1,289). Patients who had surgery in 2004, when the system and processes were reengineered, were not included in the analysis. Outcomes compared between the 2 groups included (1) acute renal failure, (2) stroke, (3) sepsis, (4) hemorrhage-related reexploration, (5) cardiac tamponade, (6) mediastinitis, and (7) prolonged length of stay. Logistic regression analysis and propensity score adjustment were used to adjust for imbalances in the patients' preoperative characteristics. After propensity score adjustment, CQI was found to decrease the rate of sepsis (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.3 to 0.9, p = 0.02) and cardiac tamponade (OR 0.2, 95% CI 0.04 to 0.8, p = 0.02) but to only marginally decrease the rate of acute renal failure (OR 0.7, 95% CI 0.5 to 1.0, p = 0.07). CQI did not emerge as an independent risk factor for hemorrhage-related reexploration, prolonged length of stay, mediastinitis, or stroke in either multivariate logistic regression analysis or propensity score adjustment. In conclusion, the systematic implementation of a CQI program and the application of multidisciplinary protocols decrease sepsis and cardiac tamponade after cardiac surgery.