This prospective, controlled trial with crossover group design compares the effectiveness of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of victims of prehospital cardiac arrest. In three UK cities, victims of non-traumatic, out of hospital cardiac arrest, over the age of 8 years received either standard or ACD-CPR on arrival of ambulance personnel. Main outcome measures were return of spontaneous circulation, survival to be admitted to the intensive care unit, survival to hospital discharge, and neurological outcome. A total of 576 patients (STD-CPR, n=309; ACD-CPR, n=267) were analysed. The treatment groups were similar with respect to age, gender, proportion of witnessed arrests, initial cardiac rhythm, and call to advanced life support interval. The proportion of patients receiving bystander CPR was higher in the ACD group (37.1% vs. 28.5%; P=0.028). The interval between collapse and defibrillation was longer in the ACD group (12.3 min vs. 10.4 min; P=0.028). There was no difference between the STD-CPR and ACD-CPR groups in survival to admission to the intensive care unit (13.6% vs. 13.8%; P=0.93) or hospital discharge (4.8% vs. 6.0%; P=0.67). There was no difference between the groups with respect to the neurological outcome of those patients surviving to hospital discharge. Analysis of important subgroups also showed no benefit for ACD-CPR. We conclude that there was no improvement in outcome with ACD-CPR when used by ambulance personnel in Cardiff and Portsmouth.