Purpose The efficacy of limited cefuroxime prophylaxis in pediatric patients after cardiovascular surgery was evaluated. Methods All patients age 18 years or younger who underwent cardiovascular surgery and received postoperative care from the cardiovascular surgery team between February and July 2006 (preintervention group) and between August 2006 and January 2007 (postintervention group) were eligible for study inclusion. Patients were excluded if they did not receive cefuroxime as postoperative prophylaxis, had a preexisting infection, underwent cardiac transplantation or extracorporeal membrane oxygenation, or underwent delayed sternal closure. The preintervention group received prolonged cefuroxime prophylaxis, and the postintervention group received 24 hours of cefuroxime prophylaxis. Data collected included patient demographics and clinical and laboratory markers of infection, as well as microbiological evidence of and treatment courses for documented or presumed infections. Results A total of 210 patients were enrolled in the study. The number of patients who required additional antibiotics for suspicion of clinical infection did not significantly differ between the preintervention and postintervention groups (18.6% versus 26.9%, respectively), nor did the rate of documented infection (bacteremia, urinary tract infection, endocarditis, sepsis) (42.1% versus 48.3%, respectively). Moreover, indications for the antibiotics initiated were similar between the preintervention and postintervention groups. Clinical and laboratory signs of postoperative infection were similar between groups. There were no differences in postoperative white blood cell counts, peak serum glucose levels, and platelet nadir between groups. Conclusion Limiting postoperative cefuroxime prophylaxis to 24 hours did not increase infectious outcomes in pediatric patients