Objectives The purpose of this study is to assess the effectiveness of defibrillation testing (DT) in patients undergoing implantable cardioverter-defibrillator (ICD) insertion. Background Although DT is considered a standard procedure during ICD implantation, its usefulness has not been definitively proven. Methods The SAFE-ICD (Safety of Two Strategies of ICD Management at Implantation) study is a prospective observational study designed to evaluate the outcome of 2 strategies: performing defibrillation testing (DT+) versus not performing defibrillation testing (DT−) during de novo ICD implants. No deviation from the centers' current practice was introduced. In all, 2,120 consecutive patients (836 DT+ and 1,284 DT−) age ≥18 years were enrolled at 41 Italian centers from April 2008 to May 2009 and followed up for 24 months until June 2011. The primary endpoint was a composite of severe complications at ICD implant and sudden cardiac death or resuscitation at 2 years. Results The primary endpoint occurred in 34 patients: 12 intraoperative complications (8 in DT+ group; 4 in DT− group) and 22 during follow-up (10 in DT+ group; 12 in DT− group). Overall, the estimated yearly incidence (95% confidence interval) was DT+ 1.15% (0.73 to 1.83) and DT− 0.68% (0.42 to 1.12). The difference between the 2 groups was negligible: 0.47% per year (−0.15 to 1.10). Mortality from any cause was similar at 2 years (adjusted hazard ratio: 0.97 0.76 to 1.23, p = 0.80). Conclusions In this large cohort of new ICD implants, event rates were similar and extremely low in both groups. These data indicate a limited clinical relevance for DT testing, thus supporting a strategy of omitting DT during an ICD implant. (Safety of Two Strategies of ICD Management at Implantation SAFE-ICD; NCT00661037 )