We assessed the incidence and prognostic significance of right bundle branch block (RBBB) in patients with acute myocardial infarction (AMI) receiving thrombolytic therapy. A prospective, one-year follow-up study involving 681 consecutive patients treated with thrombolytic agents for AMI was performed. Seventy-four patients developed RBBB (46% new-onset, 24% old and 30% indeterminate). RBBB was more common in older patients with large anterior AMI. New-onset RBBB were often transient (56%) and 84% of them resolved within 12 h after admission. Complicating events during the hospital phase, such as ventricular arrhythmias and development of heart failure, were more frequent in patients with RBBB. In-hospital and one-year mortality were higher in patients with RBBB (22.9 and 40.5% compared to 7.9 and 12.3% respectively in patients without block, both p<0.001). New-onset, non-transient RBBB were associated with the highest mortality rates (73% at one-year follow-up). By multivariate analysis, RBBB was retained as independent predictor of in-hospital and one-year mortality. We conclude that new-onset RBBB in patients receiving thrombolytic therapy for AMI is often transient. The development of RBBB has a negative and independent prognostic impact on the survival during the hospital phase and at one-year follow-up.