BACKGROUND: Active compression-decompression cardiopulmonary resuscitation (CPR) with decreased intrathoracic pressure in the decompression phase can lead to improved haemodynamics compared with standard CPR. We aimed to assess effectiveness and safety of this intervention on survival with favourable neurological function after out-of-hospital cardiac arrest. METHODS: In our randomised trial of 46 emergency medical service agencies (serving 2.3 million people) in urban, suburban, and rural areas of the USA, we assessed outcomes for patients with out-of-hospital cardiac arrest according to Utstein guidelines. We provisionally enrolled patients to receive standard CPR or active compression-decompression CPR with augmented negative intrathoracic pressure (via an impedance-threshold device) with a computer-generated block randomisation weekly schedule in a one-to-one ratio. Adults (presumed age or age >/=18 years) who had a non-traumatic arrest of presumed cardiac cause and met initial and final selection criteria received designated CPR and were included in the final analyses. The primary endpoint was survival to hospital discharge with favourable neurological function (modified Rankin scale score of