Pediatric patients with congenital heart disease can have physiologies that alter the pharmacokinetics of certain medications, such as aminoglycosides. Currently, no literature describes the appropriate dosing of aminoglycoside antibiotics for infants and children with congenital heart disease. Patients were identified through the pharmacy and laboratory computer systems. Patients were included in the study if they were younger than 18 years, received gentamicin on the acute-care (nonintensive care) cardiology floor at the authors' institution, had structural congenital heart disease, and had a peak and trough level obtained at about the third dose or later. Cohort achievement of therapeutic peak and trough concentrations based on standard dosing guidelines was evaluated. The inclusion criteria were met by 48 patients (31 boys). Eight patients (17%) had baseline cyanosis. Cardiac surgery was performed for 23 patients (48%) during the same admission at which aminoglycoside therapy was initiated. A total of 27 patients (56%) received at least one other nephrotoxic medication at the time of aminoglycoside therapy. Six patients had undetectable serum trough levels. A therapeutic peak concentration was not achieved by 16.7% of the cohort, and 7.1% of the cohort did not achieve a therapeutic trough concentration. Pediatric patients with congenital heart disease may require alterations in gentamicin dosing. Close pharmacokinetic monitoring of aminoglycoside therapy for these patients is warranted to ensure attainment of goal concentrations.