Background: Acute thrombosis is thought to contribute to abrupt coronary occlusion during percutaneous coronary revascularization despite the administration of heparin and aspirin. This study was designed to detect the presence of heparin-resistant thrombin activity and to define its relationship to the acute ischemic complications of coronary interventions. Methods and Results: Plasma levels of fibrinopeptide A (FPA) and prothrombin fragment 1.2 (F1.2), markers of thrombin and factor Xa activity, respectively, were measured in the coronary sinus with heparin-bonded catheters in 58 patients undergoing coronary interventions. Activated coagulation times were maintained >300 seconds by the Hemochron method. Mean FPA levels decreased significantly, from 7.0±0.9 nmol/L before the procedure to 5.2±0.5 nmol/L after the heparin bolus and to 2.9±0.2 nmol/L after the procedure (P=.0001). In 26 patients (45%), FPA levels remained above the threshold for suppression angioplasty of thrombin activity determined during angiography in 7 patients without coronary artery disease (>3.0 nmol/L). FPA concentrations after coronary interventions were increased in patients with intracoronary thrombus (P=.01), abrupt coronary occlusion (P=.06), postprocedural non-Q-wave myocardial infarction (P=.04), and clinically unsuccessful procedures (P=.04). F1.2 levels were relatively low before the procedures and did not change significantly. Conclusions: Heparin administration suppresses thrombin activity in most but not all patients undergoing coronary interventions. Heparin-resistant thrombin activity is associated with angiographic evidence of intracoronary thrombus and ischemic complications of coronary interventions.