Objectives. The objective of this study was to identify predictors of defibrillation threshold in patients undergoing epicardial defibrillator implantation. Background. Factors that predict epicardial defibrillation efficacy are poorly defined. Methods. The data from 375 consecutive adult patients were reviewed. After exclusion of 137 patients in whom defibrillation threshold was not obtained, 238 patients (32 women and 206 men) with a mean age of 58.9 +/- 13.3 years formed the study group. Coronary heart disease was present in 175 patients and the mean left ventricular ejection fraction was 35.8 +/- 15.4%. At device implantation, three epicardial patch sizes were available and shocks could be delivered over one current pathway (two patches) or over two current pathways (three patches with simultaneous or sequential shocks). Defibrillation threshold was defined as the lowest programmed energy that successfully defibrillated the heart, provided there had been an unsuccessful shock at a lower energy level or successful defibrillation at less-than-or-equal-to 5 J. Results. The mean defibrillation threshold was 8.6 +/- 5.3 J. With univariate analysis, female gender, sequential shocks with three patches, higher left ventricular ejection fraction and lower New York Heart Association functional class predicted a lower defibrillation threshold. In the multivariate analysis, female gender (coefficient -3.9; 95% confidence interval [CI] -1.9 to -5.0 J), ejection fraction (coefficient -0.6; CI -0.1 to -1.0 J/decile) and sequential shocks (coefficient -2.5; CI -1.0 to -4.0 J) were independently associated with a lower defibrillation threshold. Total epicardial patch conductive surface area normalized to body surface area reached borderline significance (coefficient 0.004; CI 0 to 0.01; p = 0.10). Antiarrhythmic drug use, including amiodarone, did not predict defibrillation threshold. Conclusions. Female gender, high left ventricular ejection fraction and the use of sequential pulse shocks were important determinants of improved defibrillation efficacy.