Background: During the past 50 years, novel diagnostic tools, interventional approaches, and population-wide changes in the major coronary risk factors have occurred. However, few studies have examined relatively recent trends in the demographic characteristics, clinical profile, and the short-term outcomes of patients hospitalized for acute myocardial infarction (AMI) from the more generalizable perspective of a population-based investigation. Methods:We examined decade long trends (2001 to 2011) in patient’s demographic and clinical characteristics, treatment practices, and hospital outcomes among residents of the Worcester metropolitan area hospitalized with a validated initial AMI (n = 3,730) at all 11 greater Worcester medical centers during 2001, 2003, 2005, 2007, 2009, and 2011. Results:The average age of the study population was 68.5 years and 56.9% were men. Patients hospitalized with a first AMI during the most recent study years were significantly younger (mean age = 69.9 in 2001/03; 65.2 in 2009/11), had lower serum troponin levels, and experienced a shorter hospital stay compared to patients hospitalized during the earliest study years. Hospitalized patients were more likely to received evidence-based medical management practices during the years under study. Multivariable-adjusted regression models showed a considerable decline over-time in the hospital death rate (9.6% in 2001/03; 6.5% in 2009/11), and a significant reduction in the proportion of patients who developed atrial fibrillation, heart failure, and ventricular fibrillation during their acute hospitalization. Conclusions: These results highlight the changing nature of patients hospitalized with an incident AMI, and reinforce the need for surveillance of AMI at the community level.