Aggravation of arrhythmia by antiarrhythmic drugs is a potentially serious complication. In over 1,287 noninvasive drug studies involving 11 antiarrhythmic drugs, arrhythmia aggravation occurred in 117 tests (9%). During 248 electrophysiologic tests, 45 cases (18%) of aggravation occurred. In an attempt to define predictors of this complication, 51 patients with aggravated arrhythmia were compared with 102 patients without this complication. Arrhythmia aggravation was not associated with age, sex, type or extent of heart disease, baseline electrocardiogram, drug-induced changes on electrocardiogram or density of baseline arrhythmia on monitoring or exercise testing. Aggravation with 1 drug did not predict occurrence with another drug of the same class. The only statistically important relation was the type of presenting arrhythmia. Patients with a history of a sustained tachyarrhythmia (ventricular tachycardia or ventricular fibrillation) had a risk of this complication that was 2.5 times greater than that of patients presenting with only nonsustained ventricular tachycardia or ventricular premature beats (p = 0.01). There was also a relation to the presence of left ventricular dysfunction (p = 0.04). For the most part, however, aggravation of arrhythmia is not predictable, and cautious use of antiarrhythmic drugs is essential.