Background This was a retrospective study to determine whether lack of furosemide responsiveness (LFR) predicts acute kidney injury (AKI) after cardiopulmonary bypass surgery in infants. Methods Infants (less than 1 year of age) undergoing cardiopulmonary bypass surgery, receiving routine postoperative furosemide (0.8 to 1.2 mg/kg per dose between 8 and 24 hours after surgery) were included. Urine output was measured 2 and 6 hours after furosemide dose. Lack of furosemide responsiveness was defined a priori as urine output less than 1 mL · kg−1 · h−1 after furosemide. Serum creatinine was corrected for fluid balance. Acute kidney injury was determined using changes in uncorrected and corrected serum creatinine. The predictive utility of LFR was assessed using receiver-operating characteristics curve analysis. Results We analyzed 568 infants who underwent cardiopulmonary bypass. Eighty-one (14.3%) had AKI using uncorrected serum creatinine; AKI occurred in 41 (7.2%) after correcting for fluid overload. Patients with AKI had a lower response to furosemide (median urine output 2 hours: 1.2 versus 3.4 mL · kg−1 · h−1, p = 0.01; median urine output 6 hours: 1.3 versus 2.9 mL · kg−1 · h−1, p = 0.01). After creatinine correction, LFR predicts AKI development (area under receiver-operating characteristics curve of 0.74 at 2 hours and 0.77 at 6 hours). After adjusting for surgical complexity using The Society of Thoracic Surgeons/European Association for Cardiothoracic Surgery mortality categories, the area under the receiver-operating characteristics curve was 0.74 at 2 hours and 0.81 at 6 hours. Patients with urine output greater than 1 mL · kg−1 · h−1 were unlikely to have AKI (negative predictive value, 97%). Conclusions After correcting serum creatinine for fluid balance and adjusting for surgical complexity, LFR performs fairly at 2 hours, whereas at 6 hours, LFR is a good AKI predictor. Prospective studies are needed to validate whether diuretic responsiveness predicts AKI.