BACKGROUND: Whether thrombolytic therapy alters the incidence and clinical outcome of bundle-branch block is unclear. METHODS AND RESULTS: We examined the occurrence of new-onset bundle-branch block, both transient and persistent, in 681 patients with acute myocardial infarction enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction 9 and Global Utilization of Streptokinase and t-PA for Occluded Arteries 1 protocols. Each patient underwent continuous 12-lead ECG monitoring for 36 to 72 hours with the Mortara ST monitoring system. Bundle-branch block was characterized as right, left, alternating, transient, or persistent. The overall incidence of bundle-branch block was 23.6% (n = 161), with transient block in 18.4% (n = 125) and persistent block in 5.3% (n = 36). Right bundle-branch block was found in 13% (n = 89) of the population; left bundle-branch block was found in 7% (n = 48). Alternating bundle-branch block was seen in 3.5% (n = 24) of patients. Left anterior descending artery infarcts accounted for most bundles (54%, n = 79). Patients with bundle-branch block had lower ejection fractions, higher peak creatine phosphokinase levels (P < .0001), and more diseased vessels (P < .019). Mortality rates in patients with and without bundle-branch block were 8.7% and 3.5%, respectively (P < .007). A higher mortality rate was observed in the presence of persistent (19.4%) versus transient (5.6%) or no (3.5%) bundle-branch block (P < .001). CONCLUSIONS: Thrombolytic therapy reduces the overall mortality rate associated with persistent bundle-branch block. However, persistent bundle-branch block remains predictive of a higher mortality rate than either transient or no bundle-branch block. Continuous 12-lead ECG monitoring provides an accurate characterization of the incidence and type of conduction disturbances after acute myocardial infarction.