OBJECTIVE: To determine whether the use of cardiocerebral resuscitation (CCR) or AHA/ERC 2005 Resuscitation Guidelines improved patient outcomes from out-of-hospital cardiac arrest (OHCA) compared to older guidelines. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Web of Science and the Cochrane Library databases. We also hand-searched study references and consulted experts. STUDY SELECTION: Design: randomised controlled trials and observational studies. POPULATION: OHCA patients, age >17 years. COMPARATORS: 'Control' protocol versus 'Study' protocol. 'Control' protocol defined as AHA/ERC 2000 Guidelines for cardiopulmonary resuscitation (CPR). 'Study' protocol defined as AHA/ERC 2005 Guidelines for CPR, or a CCR protocol. OUTCOME: Survival to hospital discharge. QUALITY: High-quality or medium-quality studies, as measured by the Newcastle Ottawa Scale using predefined categories. RESULTS: Twelve observational studies met inclusion criteria. All the three studies using CCR demonstrated significantly improved survival compared to use of AHA 2000 Guidelines, as did five of the nine studies using AHA/ERC 2005 Guidelines. Pooled data demonstrate that use of a CCR protocol has an unadjusted OR of 2.26 (95% CI 1.64 to 3.12) for survival to hospital discharge among all cardiac arrest patients. Among witnessed ventricular fibrillation/ventricular tachycardia (VF/VT) patients, CCR increased survival by an OR of 2.98 (95% CI 1.92 to 4.62). Studies using AHA/ERC 2005 Guidelines showed an overall trend towards increased survival, but significant heterogeneity existed among these studies. CONCLUSIONS: We demonstrate an association with improved survival from OHCA when CCR protocols or AHA/ERC 2005 Guidelines are compared to use of older guidelines. In the subgroup of patients with witnessed VF/VT, there was a threefold increase in OHCA survival when CCR was used. CCR appears to be a promising resuscitation protocol for Emergency Medical Services providers in increasing survival from OHCA. Future research will need to be conducted to directly compare AHA/ERC 2010 Guidelines with the CCR approach.