OBJECTIVE We investigated the use of blood color brightness and blood gas variables for discriminating arterial from venous puncture during cardiopulmonary resuscitation (CPR). The study's aims were to determine if discrimination using Po2 is superior to using blood color brightness, and if blood color brightness, Po2, and acid-base variables derived from blood gas analysis accurately discriminate arterial from venous blood during CPR. METHODS Fifteen pigs underwent ventricular fibrillation followed by CPR. During CPR, paired femoral arterial and venous blood samples were obtained, and 2 blinded observers were asked to identify the blood's origin. Blood color brightness was measured using a blood brightness scale (BBS). The discriminatory performances of the BBS and blood gas variables were evaluated by calculating the area under receiver operating characteristic curves (AUC). RESULTS The observers accurately discriminated arterial from venous blood with a sensitivity of 97.0% (84.7%-99.5%) and specificity of 84.9% (69.1%-93.4%). The BBS (AUC = 0.983) and Po2 (AUC = 0.981) methods both showed comparable and excellent discriminatory performances. pH, Pco2, and HCO3(-) all discriminated arterial from venous blood (AUC = 0.831, 0.971, and 0.652, respectively). The AUC for Pco2 was comparable to that for Po2 but significantly larger than that for pH (P = .002) or HCO3(-) (P < .001). CONCLUSIONS The BBS and Po2 methods showed comparable and excellent discrimination performances. Using pH, Pco2, and HCO3(-) levels also discriminated arterial from venous blood during CPR with statistical significance.