Purpose:　This　study　aimed　to　compare　the　performance　of　lactate　and　CO2-derived　parameters　in　predicting　major　postoperative　complications　(MPC)　after　cardiac　surgery　with　cardiopulmonary　bypass.　Methods:　Lactate　and　CO2-derived　parameters,　including　the　venous-arterial　difference　in　CO2　partial　pressure　(Pv-aCO(2)),　the　venous-arterial　difference　in　CO2　partial　pressure　to　arterial-venous　O-2　content　ratio　(Pv-aCO(2)/Ca-vO(2)),　and　the　venous-arterial　difference　in　CO2　content　to　arterial-venous　O-2　content　ratio　(Cv-aCO(2)/Ca-vO(2))　at　ICU　admission,　3　h,　6　h,　and　12　h　later　were　collected.　Receiver-operating　characteristics　(ROC)　curve　analysis　was　carried　out　to　assess　the　predictive　performance.　Univariate　and　multivariate　logistic　regression　analyses　were　performed　to　identify　independent　predictors　of　MPC.　Results:　MPC　occurred　in　77　(54.2%)　of　142　patients.　No　significant　difference　was　observed　between　the　MPC　and　no-MPC　groups　regarding　lactate　and　CO2-derived　parameters.　The　area　under　the　curves　(AUCs)　were　0.532　(0.446-0.616)　for　lactate,　0.559　(0.473-0.642)　for　Pv-aCO(2),　0.617　(0.532-0.697)　for　Pv-aCO(2)/Ca-vO(2),　and　0.625　(0.540-0.705)　for　Cv-aCO(2)/Ca-vO(2),　respectively,　and　there　was　no　significant　difference　between　the　parameters.　In　the　post-hoc　analysis,　all　parameters＇　AUCs　were　lower　than　0.75　in　predicting　acute　renal　failure,　and　there　was　no　significant　difference　between　these　parameters.　Cv-aCO(2)/Ca-vO(2)　at　12　h　yielded　the　highest　AUC　of　0.853　(0.784-0.907)　in　predicting　mortality　and　the　highest　AUC　of　0.808　(0.733-0.869)　in　predicting　delirium.　In　multivariate　analysis,　hypertension,　surgery　duration,　and　PaO2/FiO(2)　were　identified　as　independent　predictors　of　MPC,　while　lactate　and　CO2-derived　parameters　lost　statistical　significance　after　adjustment　for　covariates.　Conclusions:　Lactate　and　CO2-derived　parameters　cannot　be　used　as　reliable　indicators　to　predict　the　occurrence　of　MPC　after　cardiopulmonary　bypass.　Instead,　traditional　clinical　factors　such　as　hypertension,　extended　surgical　duration,　and　impaired　oxygenation　emerged　as　the　most　reliable　risk　indicators.