Cardiopulmonary resuscitation (CPR) provides possible survival from otherwise fatal cardiopulmonary collapse. Termination guidelines have been developed for use when resuscitation has no potential benefit for a victim. The purpose of this prospective cohort study was to determine if unwitnessed collapse combined with no-bystander cardiopulmonary resuscitation would support a decision to terminate attempted resuscitation. There were 541 patients analyzed during 6 months, with functional neurological survival the outcome of interest. There were no functional neurological survivors at hospital discharge among the 180 victims in the unwitnessed, no-bystander CPR subgroup (95% confidence interval [CI] 0.0%-2.1%). Functional neurological survival for witnessed collapse, bystander CPR was 6.0% (95% CI 2.8%-12.5%), for witnessed collapse, no-bystander CPR was 3.8% (95% CI 1.9%-7.7%), and for unwitnessed collapse, bystander CPR 1.3% (95% CI 0.2%-6.9%). With confirmation by further studies, unwitnessed collapse and lack of bystander CPR may be a practical addition to resuscitation termination guidelines.