Children with congenital heart disease who undergo cardiac surgery are vulnerable to acute kidney injury (AKI). This study sought to evaluate the role of angiotensin-converting enzyme (ACE) inhibitors and other nephrotoxic medications in the risk for the development of AKI in neonates and children undergoing cardiac surgery. A retrospective review of all patients younger than 2 years admitted to the cardiac intensive care unit after cardiac surgery from March 2007 to September 2008 was conducted. Patients were included in the review if they received furosemide alone or in combination with an ACE inhibitor. Creatinine clearance was calculated, and the patient's maximal degree of AKI was classified by pRIFLE. A P value less than 0.05 was considered significant. Of the 319 patients who met the inclusion criteria, 149 (47%) received furosemide therapy alone and 170 (53%) received a combination of furosemide and an ACE inhibitor. Patients in the furosemide-only group (age, 5 months) were older than the patients who received both furosemide and an ACE inhibitor (age, 3.8 months; P = 0.024). Despite statistically higher Aristotle scores in the ACE-inhibitor group, the intraoperative variables did not differ between the two groups. Postoperatively, the ACE-inhibitor group had a decreased creatinine clearance (55.3 ml/min/1.73 m(2)) compared with the furosemide group (64.4 ml/min/1.73 m(2); P = 0.015) and an increased incidence of a pRIFLE maximal score of "F" (odds ratio [OR], 1.75; P = 0.033). However, after adjustment for additional risk factors, no difference in the occurrence of AKI resulted (OR, 0.939; P = 0.85) when patients received an ACE inhibitor. More than half of the study population received ACE inhibitors, but this treatment was not associated with an increase in AKI.