This study assessed the relation between acute antiarrhythmic drug efficacy and left ventricular (LV) function in patients with sustained ventricular tachyarrhythmias, that is, sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Electrophysiologic studies (n = 560) were performed in 201 patients, separated for analysis into less than 30 and greater than or equal to 30% ejection fraction groups. Coronary artery disease was present in all patients. The 8 acute antiarrhythmic regimens were procainamide, quinidine, mexiletine, mexiletine + type 1A agent, flecainide or indecainide, amiodarone, amiodarone + type 1A and "miscellaneous" agents. At least 1 successful acute antiarrhythmic regimen was found in 47% of patients and in a significantly greater proportion of patients with ejection fraction greater than or equal to 30% (52 of 81 = 64%) than in those with ejection fraction less than 30% (43 of 120 = 36%, p less than 0.001). Drug trials were successful (initiation of less than 15 repetitive ventricular responses) in 32% of patients with ejection fraction greater than or equal to 30% versus 19% of those with ejection fraction less than 30% (p less than 0.001). There were no statistically significant differences between the 2 ejection fraction groups in type of heart disease, acute antiarrhythmic dosages or mean serum drug levels. A logistic regression analysis incorporating multiple clinically relevant factors found that ejection fraction was the only factor that correlated significantly with drug success or failure (p less than 0.002). Acute antiarrhythmic drug efficacy relates to LV function per se or to other pathophysiologic mechanisms of which ejection fraction may be a marker.