In the absence of preexistent myocardial dysfunction, the risk of producing cardiac decompensation in patients being treated with any of the conventional antiarrhythmic agents is low. The availability of disopyramide for clinical use in 1977 produced optimism for an effective antiarrhythmic agent that was free of the well-known immediate and late toxicities of quinidine and procainamide. Unfortunately, shortly after its clinical introduction, reports appeared that raised concern about the negative inotropic actions of disopyramide and the possible role of this drug in precipitating heart failure. In clinical use, the frequency of adverse effects on ventricular function appeared to be out of proportion to disopyramide's greater negative inotropic activity and the contrasting (augmenting) effect on the peripheral vascular resistance compared to that of either quinidine or procainamide, suggesting that the other factors contributed to these observations. Review of the reported literature reveals that certain factors encourage such adverse reactions. These primarily include the routine use of oral and especially intravenous loading dosages of disopyramide in an effort to attain rapid onset of action, the failure to adequately reduce dosages of disopyramide in the setting of compromised renal function, and, most importantly, the use of standard (and even loading) dosages in patients with active heart failure, compromised left ventricular function, or a history of heart failure. The avoidance of loading dosages of disopyramide, adequate reductions of maintenance dosages in the setting of renal insufficiency, gradual dose titration for additional drug action, and omission of patients with decompensated heart failure or significant left ventricular dysfunction should significantly enhance safety in the use of disopyramide.