A prospective, randomized effectiveness trial was undertaken to compare mechanical versus manual chest compressions as measured by end-tidal CO2 (ETCO2) in out-of-hospital cardiac arrest patients receiving advanced cardiac life support (ACLS) resuscitation from a municipal third-service, emergency medical services (EMS) agency. The EMS agency responds to approximately 6,700 emergencies annually, 79 of which were cardiac arrests in 1994, the study year. Following endotracheal intubation, all cardiac arrest patients were placed on 100% oxygen via the ventilator circuit of the mechanical cardiopulmonary resuscitation (CPR) device. Patients were randomized to receive mechanical CPR (TCPR) or human/manual CPR (HCPR) based on an odd/even day basis, with TCPR being performed on odd days. ETCO2 readings were obtained 5 minutes after the initiation of either TCPR or HCPR and again at the initiation of patient transport to the hospital. All patients received standard ACLS pharmacotherapy during the monitoring interval with the exception of sodium bicarbonate. CPR was continued until the patient was delivered to the hospital emergency department. Age, call response interval, initial electrocardiogram (ECG) rhythm, scene time, ETCO2 measurements, and arrest outcome were identified for all patients. Twenty patients were entered into the study, with 10 in each treatment group. Three patients in the TCPR group were excluded. Measurements in the HCPR group revealed a decreasing ETCO2 during the resuscitation in 8 of 10 patients (80%) and an increasing ETCO2 in the remaining 2 patients. No decrease in ETCO2 was noted in the TCPR group, with 4 of 7 patients (57%) actually showing an increased reading and 3 of 7 patients (43%) showing a constant ETCO2 reading. The differences in the ETCO2 measurements between TCPR and HCPR groups were statistically significant. Both groups were similar with regards to call response intervals, patient ages, scene times, and initial ECG rhythms. One patient in the TCPR group was admitted to the hospital but later died, leaving no survivors in the study. TCPR appears to be superior to standard HCPR as measured by ETCO2 in maintaining cardiac output during ACLS resuscitation of out-of-hospital cardiac arrest patients.