Aggravation of arrhythmia, defined as worsening of a preexisting arrhythmia or the occurrence of a new arrhythmia, is a common complication of antiarrhythmic drug therapy. Although it is largely an unpredictable event, patients at greatest risk are those with a history of congestive heart failure due to systolic dysfunction who present with a sustained ventricular tachyarrhythmia. As a rule, aggravation of arrhythmia is an early event, occurring within the first few days of initiating therapy. However, in the Cardiac Arrhythmia Suppression Trial (CAST), the increased sudden death mortality due to drug therapy, which was a result of arrhythmia aggravation, occurred throughout the entire duration of the trial, suggesting that arrhythmia aggravation can also be a late complication of therapy. Also disturbing was the fact that patients in CAST were low risk and did not have congestive heart failure or a serious ventricular tachyarrhythmia. This suggests that another important risk factor is myocardial ischemia and its potentially dangerous interaction with antiarrhythmic drugs. In patients with heart disease, especially those with coronary artery disease, antiarrhythmic drugs must therefore be used cautiously. Close and continuous follow-up is mandatory.