Objectives: Failure to rescue (FTR), defined as postoperative inpatient death after potentially treatable major complications, is a nationally endorsed quality of care measure, however, the effect of practice change on FTR is unknown. In this study, we aimed to define the FTR trend after cardiac surgery in the United States. Methods: In this retrospective analysis of the National Inpatient Sample database we identified adult patients who underwent cardiac surgeries in the United States between 2000 and 2018, defined incidence and trends in FTR adjusted for sex, age, diagnosis-related group, and comorbidity. Trends were analyzed us -ing Joinpoint (Statistical Methodology and Applications Branch, Surveillance Research Program, National Cancer Institute) regression software. Results: The study included 6,185,032 hospitalizations for cardiac surgeries. Risk-adjusted FTR after deep venous thromboembolism/pulmonary embolism and sepsis has declined from 2000 to 2018 (annual percent change [APC] = -6.4% and -11.6%, respectively; P < .001). After pneumonia, FTR has increased significantly since 2011 (APC = 9.3%; P <.001). Since 2012, FTR due to gastrointestinal hemor-rhage has increased substantially (APC = 15.9%; P < .001). The risk-adjusted FTR rate in patients 75 years of age or older significantly declined until 2011 (APC = -12.6%; P <.001) and became comparable with the FTR rate of younger patients by the end of the study. Conclusions: There have been significant reductions in FTR in elderly patients and a reduction in postprocedural mortality associated with sepsis and venous throm-boembolism overall after cardiac surgery. This might provide evidence supporting national targeted quality metrics and care bundles for complications such as pneu-monia and gastrointestinal bleeding, which had an increasing FTR. (J Thorac Cardi-ovasc Surg 2023;166:1157-65)