Central venous oxygen saturation has been shown to reflect the adequacy of tissue oxygenation during cardiopulmonary resuscitation (CPR), thereby enabling the assessment of CPR quality and the prediction of restoration of spontaneous circulation (ROSC). The femoral vein can be easily accessed during CPR. We determined if femoral venous oxygen saturation (S FV O 2 ) values obtained during CPR could reliably predict ROSC in a pig model.After 15 minutes of untreated ventricular fibrillation followed by 8 minutes of basic life support, 19 pigs underwent advanced cardiovascular life support. During advanced cardiovascular life support, femoral venous blood samples were obtained at 4-minute intervals. The abilities of S FV O 2 and coronary perfusion pressure (CPP) to predict ROSC were evaluated by calculating the areas under receiver operating characteristic curves (AUCs).Eight pigs (42.1%) achieved ROSC. The resuscitated animals had significantly higher CPP (P < .001) and S FV O 2 (P < .001) values than the nonresuscitated animals, and there was a significant correlation between S FV O 2 and CPP values (r = 0.684; P < .001). The CPPs of the resuscitated and nonresuscitated animals overlapped considerably; however, there was minimal overlap between the 2 groups for S FV O 2 . Femoral venous oxygen saturation significantly predicted ROSC with an AUC of 0.997 (95% confidence interval, 0.911-1.000; P < .001), and it had a larger AUC than CPP (AUC, 0.964; 95% confidence interval, 0.855-0.997; P < .001). The AUC difference, however, was not statistically significant (P = .157).In this study, S FV O 2 values obtained during CPR exhibited a significant correlation with CPP and reliably predicted ROSC.