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Although manual and semiautomatic external defibrillation (SAED) are commonly used in the management of out-of-hospital cardiac arrest, the optimal strategy is not known. We hypothesized that SAED would reduce the time to first shock and lead to higher rates of cardioversion and survival compared with a manual strategy.Between July 2005 and June 2015, we included adult out-of-hospital cardiac arrest of presumed cardiac pathogenesis. On October 2012, a treatment protocol using SAED was introduced after years of manual defibrillation. The effect of the SAED implementation on the time to first shock, successful cardioversion, and patient outcomes was assessed using interrupted time series regression adjusting for arrest factors and temporal trend. Of the 14 776 cases, 10 224 (69.2%) and 4552 (30.8%) occurred during the manual and SAED protocols, respectively. Although the proportion of patients shocked within 2 minutes of arrival increased during the SAED protocol for initial shockable rhythms (from 58.9% to 69.2%; P<0.001), there was no difference in unadjusted rate of successful cardioversion after first shock (from 12.3% to 13.8%; P=0.13). After adjustment, the odds of delivering the first shock within 2 minutes of arrival increased under the SAED protocol (adjusted odds ratio [AOR], 1.72; 95% confidence interval [CI], 1.32–2.26; P<0.001). Despite this, the SAED protocol was associated with a reduction in survival to hospital discharge (AOR, 0.71; 95% CI, 0.55–0.92; P=0.009), event survival (AOR, 0.74; 95% CI, 0.62–0.88; P=0.001), and prehospital return of spontaneous circulation (AOR, 0.81; 95% CI, 0.68–0.96; P=0.01) when compared with the manual protocol. There was also no improvement in the rate of successful cardioversion after first shock (AOR, 0.73; 95% CI, 0.51–1.06; P=0.10).Although SAED improved the time to first shock, this did not translate into higher rates of successful cardioversion or survival after out-of-hospital cardiac arrest. Advanced life support providers should be trained to use a manual defibrillation protocol.