Question What is the association of the Hospital Readmissions Reduction Program with the temporal trends in readmission and mortality rates among fee-for-service Medicare beneficiaries hospitalized with heart failure? Findings In this observational study of 115 245 fee-for-service Medicare beneficiaries hospitalized with heart failure at 416 sites across the United States, implementation of the Hospital Readmissions Reduction Program was associated with a subsequent decrease in 30-day and 1-year risk-adjusted readmissions and an increase in 30-day and 1-year risk-adjusted mortality. Meaning These findings support the possibility that the Hospital Readmissions Reduction Program has had the unintended consequence of increased mortality in patients hospitalized with heart failure. Importance Public reporting of hospitals’ 30-day risk-standardized readmission rates following heart failure hospitalization and the financial penalization of hospitals with higher rates have been associated with a reduction in 30-day readmissions but have raised concerns regarding the potential for unintended consequences. Objective To examine the association of the Hospital Readmissions Reduction Program (HRRP) with readmission and mortality outcomes among patients hospitalized with heart failure within a prospective clinical registry that allows for detailed risk adjustment. Design, Setting, and Participants Interrupted time-series and survival analyses of index heart failure hospitalizations were conducted from January 1, 2006, to December 31, 2014. This study included 115 245 fee-for-service Medicare beneficiaries across 416 US hospital sites participating in the American Heart Association Get With The Guidelines-Heart Failure registry. Data analysis took place from January 1, 2017, to June 8, 2017. Exposures Time intervals related to the HRRP were before the HRRP implementation (January 1, 2006, to March 31, 2010), during the HRRP implementation (April 1, 2010, to September 30, 2012), and after the HRRP penalties went into effect (October 1, 2012, to December 31, 2014). Main Outcomes and Measures Risk-adjusted 30-day and 1-year all-cause readmission and mortality rates. Results The mean (SD) age of the study population (n = 115 245) was 80.5 (8.4) years, 62 927 (54.6%) were women, and 91 996 (81.3%) were white and 11 037 (9.7%) were black. The 30-day risk-adjusted readmission rate declined from 20.0% before the HRRP implementation to 18.4% in the HRRP penalties phase (hazard ratio (HR) after vs before the HRRP implementation, 0.91; 95% CI, 0.87-0.95; P < .001). In contrast, the 30-day risk-adjusted mortality rate increased from 7.2% before the HRRP implementation to 8.6% in the HRRP penalties phase (HR after vs before the HRRP implementation, 1.18; 95% CI, 1.10-1.27; P < .001). The 1-year risk-adjusted readmission and mortality rates followed a similar pattern as the 30-day outcomes. The 1-year risk-adjusted readmission rate declined from 57.2% to 56.3% (HR, 0.92; 95% CI, 0.89-0.96; P < .001), and the 1-year risk-adjusted mortality rate increased from 31.3% to 36.3% (HR, 1.10; 95% CI, 1.06-1.14; P < .001) after vs before the HRRP implementation. Conclusions and Relevance Among fee-for-service Medicare beneficiaries discharged after heart failure hospitalizations, implementation of the HRRP was temporally associated with a reduction in 30-day and 1-year readmissions but an increase in 30-day and 1-year mortality. If confirmed, this finding may require reconsideration of the HRRP in heart failure. Using data from the American Heart Association Get With The Guidelines-Heart Failure program registry, this observational study conducts interrupted time series and survival analyses to determine the association between the implementation of the Hospital Readmissions Reduction Program and readmission and mortality outcomes among patients hospitalized with heart failure.