Approximately 1.5 million individuals experience a myocardial infarction (MI) each year in the United States. Of these, 20% develop major depression (MDD) and are at increased risk of re-infarction, overall morbidity and mortality. OBJECTIVE: The objective of this study was to compare the health care costs and resource utilization for patients diagnosed with MI + MDD with patients with MI only, MDD only and a control group having neither condition. METHODS: Claims data for all patients at least 40 years of age from a large HMO in the Southeast US were analyzed retrospectively. Patients were selected for study if they had an incident event of MI, MDD, or MI+MDD during a one-year recruitment period. Age and sex matched patients having neither MI nor MDD during the recruitment period served as the control group. Patients were followed for two years from their dates of recruitment. Patients were included in the MI+MDD group only if they had at least six months of data for analysis. Only patients with drug charges were included for final evaluation. RESULTS: Compared with $6,877 for patients in the control group (n=436), mean total costs were statistically different for each group, including $13,982 for MDD patients (n=296), $35,589 for MI patients (n=98), and $57,835 for MI+MDD patients (n=53). Significant differences between the groups were found for the number of hospitalizations, length of hospital stay, outpatient visits, types of prescribed medication, and number of filled prescriptions. Other significant differences between groups included their need for therapeutic drug assays, particularly digoxin, and cardiovascular laboratory procedures, particularly the use of devices to monitor for arrhythmia. CONCLUSION: The cost of illness and resource utilization for patients who had MI+MDD are much greater than patients having MI or MDD alone. Early recognition of patients with MI+MDD is warranted.