BACKGROUND: Cardiopulmonary resuscitation (CPR) creates artifacts on the ECG and, with automated defibrillators, a pause in CPR is mandatory during rhythm analysis. The rate of return of spontaneous circulation (ROSC) is reduced with increased duration of this hands-off interval in rats. We analyzed whether similar hands-off intervals in humans with ventricular fibrillation causes changes in the ECG predicting a lower probability of ROSC. METHODS AND RESULTS: The probability of ROSC after a shock was continually determined from ECG signal characteristics for up to 20 seconds of 634 such hands-off intervals in patients with ventricular fibrillation. In hands-off intervals with an initially high (40% to 100%) or median (25% to 40%) probability for ROSC, the probability was gradually reduced with time to a median of 8% to 11% after 20 seconds (P