BACKGROUND:Inability to resume employment after acute myocardial infarction (MI) has important implications for patients. We sought to assess the prevalence of and outcomes associated with adverse change in employment after MI in a national US cohort. METHODS AND RESULTS:The TRANSLATE-ACS study (Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome) assessed employment status at baseline and 1 year among 9319 patients with MI (mean age, 60.8 years; SD, 11.3; 27.3% women) enrolled at 233 US hospitals. We defined adverse change in employment as patients working at baseline but working less or not working at 1-year post-MI. In multivariable models, we assessed factors associated with adverse change in employment and its association with patient-reported depression, health status, persistence to evidence-based medications prescribed at discharge, and financial hardship affording medications. Half of the patients (51%; n=4730) were employed at the time of MI. By 1 year, 10% (n=492) of these reported an adverse change in employment, with 3% (n=143) working less and 7% (n=349) no longer working (only 27 of 349 reported retirement). Factors significantly associated with adverse change in employment included a number of unplanned readmissions, postdischarge bleeding complications, hypertension, and smoking. At 1 year, patients with an adverse change in employment were more likely to report depression (Patient Health Questionnaire 2 score >3: 27.4% versus 16.7%), lower health status (mean EuroQoL visual analogue scale: 73 [SD, 17.8] versus 78 [SD, 14.8]), and moderate-extreme financial hardship with medication costs (41.0% versus 28.4%; all P<0.001). There was no difference in persistence to evidence-based medications prescribed at discharge. CONCLUSIONS:Patients who experienced an adverse change in employment after MI reported lower quality of life, increased depression, and more difficulty affording medications. These results underscore the need for interventions to address this patient-centered outcome and its health impact. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.