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Background— During out-of-hospital cardiac arrest, it is unclear how long prehospital resuscitation efforts should be continued to maximize lives saved. Methods and Results— Between 2005 and 2012, we enrolled 282 183 adult patients with bystander-witnessed out-of-hospital cardiac arrest from the All-Japan Utstein Registry. Prehospital resuscitation duration was calculated as the time interval from call receipt to return of spontaneous circulation in cases achieving prehospital return of spontaneous circulation or from call receipt to hospital arrival in cases not achieving prehospital return of spontaneous circulation. In each of 4 groups stratified by initial cardiac arrest rhythm (shockable versus nonshockable) and bystander resuscitation (presence versus absence), we calculated minimum prehospital resuscitation duration, defined as the length of resuscitation efforts in minutes required to achieve ≥99% sensitivity for the primary end point, favorable 30-day neurological outcome after out-of-hospital cardiac arrest. Prehospital resuscitation duration to achieve prehospital return of spontaneous circulation ranged from 1 to 60 minutes. Longer prehospital resuscitation duration reduced the likelihood of favorable neurological outcome (adjusted odds ratio, 0.84; 95% confidence interval, 0.838–0.844). Although the frequency of favorable neurological outcome was significantly different among the 4 groups, ranging from 20.0% (shockable/bystander resuscitation group) to 0.9% (nonshockable/bystander resuscitation group; P <0.001), minimum prehospital resuscitation duration did not differ widely among the 4 groups (40 minutes in the shockable/bystander resuscitation group and the shockable/no bystander resuscitation group, 44 minutes in the nonshockable/bystander resuscitation group, and 45 minutes in the nonshockable/no bystander resuscitation group). Conclusions— On the basis of time intervals from the shockable arrest groups, prehospital resuscitation efforts should be continued for at least 40 minutes in all adults with bystander-witnessed out-of-hospital cardiac arrest. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/ . Unique identifier: 000009918.