OBJECTIVE: To assess the health economic impact of perioperative myocardial infarction in a cohort of patients undergoing coronary artery bypass graft surgery. DESIGN: Retrospective cohort analysis using data from hospital bills and uniform billing forms. SETTING: A total of 147 geographically diverse hospitals in the United States. PATIENTS: The study population consisted of 2,102 coronary artery bypass graft surgery patients enrolled in the PRIMO-CABG trial at U.S. sites between January 2002 and February 2003. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Resource utilization and costs during the index hospitalization and during a 6-month follow-up period were compared between patients who had a myocardial infarction by postoperative day 4 and those who did not. Linear regression was used to examine whether myocardial infarction by day 4 was associated with index hospitalization costs, after adjusting for baseline characteristics. Myocardial infarction occurred in 191 (9.1%) patients undergoing coronary artery bypass graft surgery. Myocardial infarction was associated with a doubling of intensive care unit time (3.5 days among patients with no myocardial infarction and 7.1 days among patients with myocardial infarction, p < .01) and a 48% increase in hospital length of stay. Myocardial infarction by day 4 was associated with a 43% increase in hospital costs, a 29% increase in physician service costs, a 41% increase in total costs during the index hospitalization, and a 38% increase in cumulative 6-month costs. After baseline adjustment, myocardial infarction continued to be associated with higher index hospitalization costs. CONCLUSIONS: Myocardial infarction following coronary artery bypass graft surgery was associated with a significant increase in intensive care unit time, hospital length of stay, and overall costs, which contributed to greater hospital and physician service costs. Healthcare resource utilization is increased in patients sustaining a myocardial infarction following coronary artery bypass graft surgery. © 2007 Lippincott Williams & Wilkins, Inc.