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Background: The implantable cardioverter--defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential adverse effects. Methods: We randomly assigned 1500 patients with a primary-prevention indication to receive an ICD with one of three programming configurations. The primary objective was to determine whether programmed high-rate therapy (with a 2.5-second delay before the initiation of therapy at a heart rate of ≥ 200 beats per minute) or delayed therapy (with a 60-second delay at 170 to 199 beats per minute, a 12-second delay at 200 to 249 beats per minute, and a 2.5-second delay at ≥ 250 beats per minute) was associated with a decrease in the number of patients with a first occurrence of inappropriate antitachycardia pacing or shocks, as compared with conventional programming (with a 2.5-second delay at 170 to 199 beats per minute and a 1.0-second delay at ≥ 200 beats per minute). Results: During an average follow-up of 1.4 years, highrate therapy and delayed ICD therapy, as compared with conventional device programming, were associated with reductions in a first occurrence of inappropriate therapy (hazard ratio with high-rate therapy vs. conventional therapy, 0.21; 95% confidence interval [CI], 0.13 to 0.34; P < 0.001; hazard ratio with delayed therapy vs. conventional therapy, 0.24; 95% CI, 0.15 to 0.40; P < 0.001) and reductions in all-cause mortality (hazard ratio with high-rate therapy vs. conventional therapy, 0.45; 95% CI, 0.24 to 0.85; P = 0.01; hazard ratio with delayed therapy vs. conventional therapy, 0.56; 95% CI, 0.30 to 1.02; P = 0.06). There were no significant differences in procedure-related adverse events among the three treatment groups. Conclusions: Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher, as compared with conventional programming, was associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up. (Funded by Boston Scientific; MADIT-RIT ClinicalTrials.gov number, NCT00947310).

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