Cardiopulmonary bypass-associated acute kidney injury may appear postoperatively, but predictive factors are unclear. We investigated the potential of regional tissue oxygen saturation as a predictor of cardiopulmonary bypass-associated acute kidney injury. We analyzed the clinical data of 150 adult patients not on dialysis who underwent elective cardiac surgical procedures during January 2015-March 2017. Near-infrared spectroscopy was used to measure regional oxygen saturation. Sensors were placed on the patients' forehead, abdomen, and thigh. The incidence of acute kidney injury was 2% at the end of surgery, 13% at 24 h, and 9% at 48 h, with the highest at 24 h after surgery. The multiple regression analysis revealed that the thigh regional oximetry during cardiopulmonary bypass, oxygen delivery index, and neutrophil count at the end of cardiopulmonary bypass and surgery were independent risk factors for acute kidney injury. The receiver-operating characteristic curve analysis suggested that a cutoff of regional oxygen saturation at the thigh of ≤ 67% was predictive of acute kidney injury within 24 h after surgery. In conclusion, the regional oxygen saturation at the thigh during cardiopulmonary bypass is a crucial marker to predict postoperative acute kidney injury in adults undergoing cardiac surgery.