Background: The primary analysis of a clinical trial comparing active compression decompression cardiopulmonary resuscitation (CPR) plus an impedance threshold device (ACD+ITD) with standard (S) CPR in subjects with non-traumatic out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology (n=1653) showed that ACD+ITD resulted in improved survival to hospital discharge with favorable neurologic function. In that evaluation, nearly one third of all patients treated with either S-CPR or ACD+ITD did not meet final enrollment criteria. Safety and effectiveness findings from all randomized subjects in that trial, regardless of OHCA etiology, are described herein. Methods & Results: Adults with presumed non-traumatic OHCA were prospectively enrolled and randomly allocated to treatment with S-CPR (N=1335) or ACD+ITD (N=1403). Except for rescue personnel, research and hospital staff were blinded to treatment assignment. The primary endpoint was survival to discharge with favorable neurologic function (modified Rankin Scale score ?3). Survival to discharge with favorable neurologic function was greater with ACD+ITD compared with S-CPR: 7.9% versus 5.7%, (OR 1.42, 95% CI 1.04,1.95, p=0.027). One-year survival was also greater: 7.9% versus 5.7%, (OR 1.43, 95% CI 1.04,1.96, p=0.026). Nearly all survivors in both groups had returned to their baseline neurological function by one year. Major adverse event rates were similar between groups. Conclusions: ACD+ITD resulted in a 38% increase in survival with favorable neurological function at hospital discharge, and a 39% increase in survival at one year. These findings from all randomized study subjects, regardless of OHCA etiology, support the use of ACD+ITD in all non-traumatic cardiac arrest patients.