Inflammation may play an important role in acute coronary syndromes. We studied the prognostic value of fibrinogen, an acute-phase protein directly involved in thrombotic process, measured serially in 1,473 patients with unstable angina and non-Q-wave myocardial infarction participating in the Thrombolysis in Myocardial Infarction IIIB trial. Overall, no association was found between baseline (pretreatment) fibrinogen and in-hospital (< or = 10 days) myocardial infarction (p=0.70) and death (p=0.64); however, patients with spontaneous ischemia (p=0.004) and the combined unsatisfactory outcome of death, myocardial infarction, and spontaneous ischemia (p=0.003) had higher fibrinogen concentrations than those without these events. This association was confined to patients with unstable angina. A baseline fibrinogen concentration > or = 300 mg/dl was associated with a modest trend toward an increased risk of death, myocardial infarction, or spontaneous ischemia (odds ratio 1.61, 95% confidence interval 1.02 to 2.52; p=0.04). Elevation of fibrinogen, a readily measurable acute-phase protein, at the time of hospital admission is associated with coronary ischemic events and a poor clinical outcome in patients with unstable angina.