BACKGROUND The subcutaneous implantable cardioverter-defibrillator system (S-ICD) uses a novel detection algorithm previously shown to discriminate induced tachyarrhythmias (ventricular vs supraventricular) effectively. OBJECTIVE The purpose of this study was to evaluate the role of the S-ICD discrimination algorithm in reducing the incidence of spontaneous inappropriate shocks. METHODS A total of 314 subjects underwent implantation with an S-ICD system as part of the S-ICD Clinical Investigation (IDE Trial). Subjects were grouped according to programming at discharge to either a single shock zone or 2 shock zones, with a discrimination algorithm in the lower rate zone. RESULTS This cohort had 226 subjects (72%) with dual zone programming and 88 subjects (28%) with single zone programming. Over a mean follow-up period of 661 +/- 174 days, inappropriate shocks occurred in 23 subjects from the dual zone subgroup (10.2%) and 23 subjects from the single zone subgroup (26.1%, P < .001), with 2-year inappropriate shock-free rates of 89.7% vs 73.6%;,respectively (hazard ratio 0.38, P = .001). Freedom from appropriate shocks did not differ between subgroups (92.2% vs 90.3%, hazard ratio 0.82, P = .64). Moreover, mean time to appropriate therapy did not differ between subgroups, and there was only 1 episode of arrhythmic syncope in the cohort. CONCLUSION The addition of a second shock zone with an active discrimination algorithm was strongly associated with a reduction in inappropriate shocks with the S-ICD system and did not result in prolongation of detection times or increased syncope. These data support the use of dual zone programming as a standard setting for S-ICD patients.