Newly developed biphasic waveforms improve defibrillation efficacy both by reduction of defibrillation threshold and by amelioration of shock-induced dysfunction depending on the relative shape of the first and second pulses. Each of these independent effects improves the waveform's safety factor, the ratio between the shock intensity that produces a specific degree of postshock dysfunction and the shock intensity that produces defibrillation (or cellular excitation). Symmetrical waveforms reduce defibrillation threshold to about 60percent; that of the corresponding monophasic waveform, probably by reduction of excitation threshold for ischemic cells, but increase postshock arrhythmias. Biphasic waveforms with 10percent; "tails" reduce postshock arrhythmias. This study tests the hypothesis that these independent mechanisms for improvement of defibrillation efficacy can be combined into a single triphasic waveform that will have a highers afety factor than either of the two biphasic waveforms of which it is composed. Cultured myocardial cells were subjected to high-intensity electric-field stimulation with a control monophasic rectangular waveform, a symmetrical biphasic waveform, and a triphasic waveform consisting of the biphasic waveform with an added 10percent; "tail." Each waveform portion was 5 msec in duration. Photocell mechanograms monitored contractile activity. We found that the duration of postshock arrest of spontaneous contractile activity increased with stimulus intensity for all waveforms. The voltage gradient producing a 4-second arrest after the biphasic waveform shock was 80.6±1.3percent; that of the control waveform (100percent;), while the voltage gradient for the triphasic waveform was 87.1 ±0.73percent; of control. The difference between biphasic and triphasic waveforms was significant (p<0.001). Relative excitation thresholds for the biphasic and triphasic waveforms were each 67percent; that of the monophasic waveform and did not differ significantly. Relative safety factor for the biphasic waveform was 120.3 and that for the triphasic waveform was 130.0 compared with a value of 100 for the control monophasic waveform. These results suggest that triphasic waveforms decrease postshock arrhythmias and increase the safety factor for defibrillation.