The use of magnesium in patients with acute myocardial infarction (AMI) is debated, largely as a result of conflicting data from randomized controlled trials. This study evaluated the use and impact on mortality of intravenous magnesium in the treatment of patients with AMI in the United States based on data from the Second National Registry of Myocardial Infarction. Only 5.1% of 173,728 patients from 1,326 hospitals received intravenous magnesium within the first 24 hours after an AMI, and this was more common in the 59,798 patients who received thrombolytic therapy or who underwent primary percutaneous transluminal coronary angioplasty (PTCA) or coronary bypass grafting (CABG) than in the 113,930 patients who did not receive any reperfusion therapy (8.5% vs 3.4%, p <0.01). Magnesium use was associated with younger age, Q-wave AMI, congestive heart failure on admission, thrombolytic therapy, primary PTCA or CABG, ventricular tachycardia or ventricular fibrillation, and beta blocker or lidocaine use in the first 24 hours (all odds ratio > 1.2, p <0.001). Magnesium use was associated with increased mortality (odds ratio 1.25, 95% confidence interval 1.12 to 1.34) and with a higher mortality in patients without initial reperfusion therapy (20.2% vs 13.2%, p <0.0001) or who underwent primary PTCA or CABG (10.2% vs 7.3%, p = 0.002), but not in patients who received thrombolytic therapy (6.2% vs 5.9%, p = NS). Thus, magnesium is used infrequently in the treatment of AMI and may be associated with worse outcome.