The proarrhythmic effects of cocaine may be mediated in part by its effects on cardiac repolarization properties. This study evaluated the acute effects of smoking cocaine 25 mg on the electrocardiograms of 14 habitual cocaine users during a 12-minute observation period. After cocaine administration, heart rate increased by a mean of 22 beats/min (p <0.0001). One patient developed accelerated junctional rhythm, and 5 had nonspecific ST-T-wave abnormalities. The electrocardiograms revealed significant prolongation of the QTc interval (p <0.001) after cocaine administration. In addition, T-wave amplitude decreased and U-wave amplitude increased in response to cocaine use (p <0.05). QRS duration was unchanged by cocaine, whereas the PR interval shortened slightly. The repolarization changes observed after cocaine use were similar to those reported for other sympathomimetic agents and may be a contributing factor in the association between cocaine use and ventricular arrhythmias.