Background: In epidemiologic studies, excessive body weight, independent of other risk factors, portends a poor prognosis among patients with coronary artery disease experiencing acute myocardial infarction (MI). At least one recent study has suggested that patients of excessive body weight when receiving thrombolytic therapy are often underdosed, potentially reducing early coronary arterial patency and adversely affecting in-hospital clinical outcome. Concern has also been raised that body weight may influence treatment utilization, delays, and complication rates. Despite these concerns, the association between body weight and patient outcome following coronary thrombolysis has received limited attention. Methods/Results: Demographic, procedural, and outcome data from patients with MI were collected at 1073 United States hospitals participating in The National Registry of Myocardial Infarction from 1990 through 1994. Among 350,755 patients with MI enrolled, 87,688 (25.1%) were treated with tissue plasminogen activator (t-PA). Divided into body weight tertiles, 23.5% of patients were less than 70 kg (low weight), 36.8% were 70–85 kg (modrate weight), and 37.5% were greater than 85 kg (high weight). Patients of low weight were older (p < 0.001), received treatment later (p < 0.001), and were less likely to undergo cardiac catheterization, coronary angioplasty, or bypass surgery (p < 0.001) than moderate- or high-weight patients. Low-weight patients also experienced minor bleeding, major bleeding, recurrent MI, and death more often (p < 0.001). Adjusted for age, low body weight was independently associated with in-hospital mortality. Despite receiving a lower dose of t-PA per kg body weight, high-weight patients had a low incidence of cardiogenic shock, recurrent MI, death, and hemorrhagic complications. When high-weight women and men were compared, several interesting observations emerged. Mortality was increased twofold in women (6.8% vs. 3.0; p < 0.001), even adjusting for their older age. Despite being at increased risk, women were less likely than their male counterparts to undergo cardiac catheterization (p=0.001) or bypass surgery (p=0.008). Conclusions: The National Registry of Myocardial Infarction provides a unique resource for assessing health care trends in the United States. Our findings suggest that low body weight is associated with increased in-hospital morbidity and mortality. They also suggest that current dosing strategies for t-PA administration are probably adequate for high-weight patients. The excessive mortality and limited use of in-hospital interventions among high-weight women deserve further study to address gender-related differences in disease processes, as well as potential bias or discrimination. © 1996, Kluwer Academic Publishers. All rights reserved.