The dosing of anticoagulants during coronary angioplasty is commonly guided by measurements of activated clotting time (ACT), but the usefulness of these measurements remains uncertain. The Hirulog Angioplasty Study was a randomized, double-blind comparison of heparin versus bivalirudin in 4,312 patients undergoing angioplasty for unstable or postinfarction angina. In 4,098 of the patients randomized, the balloon was inflated. All patients had ACT measurements 5 minutes after a weight-adjusted bolus of heparin or bivalirudin, and patients undergoing complicated or prolonged angioplasty procedures lasting >45 minutes had additional ACT measurements to guide further anticoagulant therapy. The analysis presented in this article evaluated the relation between the initial or maximum ACT measurements and the risk of abrupt vessel closure during heparin or bivalirudin therapy. Abrupt vessel closure occurred in 189 of 2,039 patients (9.3%) treated with heparin, and in 189 of 2,059 patients (9.2%) treated with bivalirudin (p = not significant). An inverse relation between the risk of abrupt closure and initial ACT measurements was observed in heparin-treated patients: the probability of abrupt vessel closure decreased by 1.3% for every 10-second increase in the initial ACT response to heparin therapy (p = 0.02). Among 903 of 2,039 heparin-treated patients (44%) who received additional heparin for prolonged or complicated procedures, the likelihood of abrupt vessel closure also decreased by 1.1% for every 10-second increase in ACT (p = 0.04). In 2,059 patients treated with bivalirudin, however, no relation between the probability of abrupt vessel closure and the initial ACT measurement was observed (p = 0.88). From the results it was concluded that when heparin is used during coronary angioplasty, the risk of abrupt vessel closure is related to patient responsiveness to anticoagulation therapy. Heparin-resistant patients are more likely to experience abrupt vessel closure than patients who have high ACT values in response to initial therapy. In contrast, when bivalirudin is used during coronary angioplasty, a flat relation between the risk of abrupt vessel closure and ACT values is seen. This suggests that the direct thrombin inhibitor, bivalirudin, provides more even levels of anticoagulation and more predictable levels of risk of abrupt closure than heparin. Measurements of ACT may not be necessary when bivalirudin is used during coronary angioplasty.