Despite the magnitude and impact of acute coronary disease, there are limited population-based data in the United States describing relatively recent trends in the incidence rates of acute myocardial infarction (AMI). The objectives of this study were to describe decade long (2001-2011) trends in the incidence rates of initial hospitalized episodes of AMI, with further stratification of these rates by age, sex, and type of AMI, in residents of central Massachusetts hospitalized at 11 area medical centers. The study population consisted of 3,737 adults hospitalized with a first AMI at 11 medical centers in central Massachusetts on a biennial basis between 2001 and 2011. The median age of this study population was 70 years, 57% were men, and 90% were white. Patients hospitalized during the most recent study years (2009/11) were younger, more likely to be men, have more co-morbidities, and less in-hospital complications as compared with those in the earliest study years (2001/03). The overall age-adjusted hospital incidence rates (per 100,000 persons) of initial AMI declined (from 319 to 163), for men (from 422 to 219), women (from 232 to 120), for patients with a ST segment elevation (129 to 56), and for those with an non-ST segment elevation (190 to 107) between 2001 and 2011, respectively. In conclusion, the incidence rates of initial AMI declined appreciably in residents of central Massachusetts who were hospitalized with AMI during the years under study.