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Background: Reducing hospital readmission after acute myocardial infarction (AMI) has the potential to both improve quality and reduce costs. As such, readmission after AMI has been a target of financial penalties through Medicare. However, substantial concern exists about potential adverse effects and efficacious readmission-reduction strategies are not well validated., Methods and Results: We started an AMI readmissions reduction program in November 2017. Between July 2016 and February 2019, hospital billing data were queried to detect all inpatient hospitalizations at the Massachusetts General Hospital for AMI. Thirty-day readmission was identified through hospital billing data, and mortality was extracted from our electronic health record. The data set was merged with claims data for patients in accountable care organizations to detect readmission at other hospitals. We performed segmented linear regression, adjusting for secular trend and case mix, to assess the independent association of our program on both outcome variables. After inclusion and exclusion criteria were applied, the study population included 2020 patients. The overall 30-day readmission rate was higher before the intervention than after the intervention (15.5% versus 10.7%, P =0.002). The overall 30-day mortality rate was similar in both time periods (1.8% versus 1.4%, P =0.457). The program was associated with initial reduction in 30-day readmission (-9.8%, P =0.0002) and 30-day mortality (-2.6%, P =0.041). The program did not change trend in 30-day readmission (+0.19% readmissions/mo, P =0.554) and trend in 30-day mortality (-0.21% deaths/mo, P =0.119)., Conclusions: An AMI readmissions reduction program that increases outpatient and emergency department (ED) access to cardiology care is associated with reduced 30-day readmission and 30-day mortality. Similar statistical techniques can be used to conduct a rigorous, mechanistic program evaluation of other quality improvement initiatives.