Background: Women with acute myocardial infarction are more likely than men to experience reinfarction, bleeding, or death. This difference has been hypothesized to be due to older age, treatment delay, and comorbidities in women. Use of diagnostic and therapeutic modalities may also differ. There is controversy regarding whether female sex is an independent risk factor for death and/or bleeding. Methods: The GUSTO (Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes) V Investigators studied standard-dose reteplase vs standard-dose abciximab plus half-dose reteplase in patients with myocardial infarction. Results: Women were older and more often had diabetes mellitus and hypertension. Angiography and percutaneous coronary intervention were less frequent in women. Death (9.8% vs 4.4% at 30 days, odds ratio [OR], 2.00, 95% confidence interval, 1.59-2.53,P < .001) and bleeding (6.4% vs 2.5%, OR, 1.31, 95% confidence interval, 1.18-1.45, P < .01) were more common in women. There was no association between treatment assignment and death in either sex, bleeding was more common in both sexes receiving combination therapy. Female sex was independently associated with mortality. After Killip class greater than 1 (OR, 4.7), female sex (OR, 2.0) was the strongest correlate of death. Female sex was independently associated with bleeding for both treatments. Conclusions: Female sex is independently associated with death and bleeding complications among fibrinolytic-treated patients with myocardial infarction. There remains a sex differential in the use of angiography and, therefore, percutaneous coronary intervention after fibrinolysis. Further research will determine what mediates excess risk in women. Trial Registration: clinicaltrials.gov Identifier: NCT00245648. ©2007 American Medical Association. All rights reserved.