This study aimed to develop a new risk-adjustment method to assess acute myocardial infarction (AMI) in-hospital mortality. Risk-adjustment was based on variables obtained from administrative data from Japanese hospitals, and included factors such as age, gender, primary diagnosis and co-morbidity. The infarct location was determined using the criteria of the International Classification of Diseases (10th version). Potential comorbidity risk factors for mortality were selected based on previous studies and their critical influence analysed to identify major co-morbidities. The remaining minor co-morbidities were then divided into two groups based on their medical implications. The major co-morbidities included shock, pneumonia, cancer and chronic renal failure. The two minor co-morbidity groups also demonstrated a substantial impact on mortality. The model was then used to assess clinical performance in the participating hospitals. Our model reliably employed the available data for the risk-adjustment of AMI mortality and provides a new approach to evaluating clinical performance.