Serial DFT Measures in Man.Introduction;The defibrillation threshold (DFT) may change throughout the first year following implantation of a cardioverter defibrillator, but it remains uncertain if changes are a consequence of changes in clinical condition or are related to fundamental alterations at the electrode‐tissue interface. The purpose of this study was to evaluate the extent and time course of DFT changes over the first year following implantable cardioverter defibrillator (ICD) surgery when extraneous clinical and device variables potentially affecting the DFT were excluded.Methods and Results.: We prospectively enrolled 61 patients undergoing epicardial or non‐thoracotomy/transvenous ICD therapy into a series of follow‐up studies where the DFT was measured at implant and at 1, 6,12, and 52 weeks following implantation in a uniform manner. Stored energy DFT was measured and recorded for all patients. Patient exclusion criteria were: (1) inability to complete all five measures of the DFT; (2) institution of Class I or Class III antiarrhythmic drugs at any time during the study; (3) lead system changes (relocation or new leads) or programming changes in pulse width or current pathway; or (4) development of a significant change in their clinical status, such as decompensated congestive heart failure or acute ischemia. Only 20 of the 61 patients satisfied the criteria required to complete the study. Two of the excluded patients developed high DFTs, which required reprogramming of the current pathway. Eight patients had an epicardial lead system, and 12 had a nonthoracotomy lead system. The rise in DFT over the first 12 weeks was significant for the eight epicardial lead system patients (P = 0.05) and for the 12 nonthoracotomy lead system patients (P = 0.004). The peak rise in DFT occurred at 1 week for the patients with an epicardial lead system (3.4 ± 1.8 J to 7.9 ± 3.8 J) and at 12 weeks for the patients with a transvenous lead system (10.3 ± 5.3 J to 16.1 ± 7.4 J).Conclusions: This study confirms a transient significant rise in the DFT in the first 12 weeks following ICD surgery that partially returns to the implant value over the remainder of the year. Because specific clinical and technical variables were excluded from this study, the observations made in this patient population suggest that the rise in DFT may be a consequence of changes at the electrode‐tissu