Background: Among adults with heart disease, there is a high prevalence of concomitant chronic medical conditions. We studied patients with a first acute myocardial infarction to describe: sample population characteristics; trends of the most prevalent pairs of chronic conditions; and differences in hospital management according to burden of these morbidities. Methods and Results: Patients (n = 1,564) hospitalized with an incident AMI at the 3 major medical centers in central Massachusetts during 2005, 2011, and 2015 comprised the study population. Hospital medical records were reviewed to identify 11 more prevalent chronic conditions. The median age of this population was 68 years and 56% were men. The median number of previously diagnosed chronic conditions was 2. Patients hospitalized during 2015 were more likely to be younger than those hospitalized in the earliest study cohorts. The most common pairs of chronic conditions for those hospitalized in 2005 were: anemia-chronic kidney disease (31%), chronic kidney disease-heart failure (30%), and stroke-atrial fibrillation (27%). Among patients hospitalized during 2011, chronic kidney disease-heart failure (29%), hypertension-hyperlipidemia (27%), and hypertension-diabetes (27%) were the most common pairs whereas hypertension-hyperlipidemia (43%), diabetes-heart failure (30%), and chronic kidney disease-diabetes (23%) were the most frequent pairs recorded in 2015. There was a significant decrease in the odds of undergoing cardiac catheterization and a percutaneous coronary intervention in those with higher chronic disease burden in the most recent as compared to earliest study years. Conclusions: Our findings highlight the magnitude of chronic conditions in patients with AMI and the challenges of caring for this vulnerable population.