The ideal duration of postoperative antibiotic prophylaxis in heart surgery is unknown. The most recent guidelines recommend a decrease in prophylaxis time to decrease the emergence of multiresistant germs. However, compliance with these recommendations is scant. Our aim was to determine whether a decrease in prophylaxis time entails an increase in the infection rate. A retrospective study was performed between September 2003 and March 2006, including all patients of ages between 1 day and 14 years who were admitted to the intensive care unit after heart surgery. Patients being treated for an infection at the time of surgery were excluded. The appearance of nosocomial infection, localisation, and the causative agent, if isolated, were included; demographic and clinical analytical variables, duration and type of antibiotic prophylaxis, and duration of other invasive devices were also included. Standard analysis and multivariable logistical regression were performed. 194 patients were included in the study. The median duration of antibiotic prophylaxis was 72 h (range 24 to 176), with the most-used prophylaxis regimen being second-generation cephalosporins plus aminoglycosides. The incidence of nosocomial infection, mainly bacteraemia, was 11.9%. The type of antibiotic therapy used for prophylaxis did not affect the incidence of infection. In the multivariable logistical regression, only prolongation of antibiotic prophylaxis >48 h, central venous access maintenance time, and intubation increased the infection rate. The suspension of antibiotic prophylaxis in the 48 h after surgery in pediatric patients undergoing heart surgery does not increase the incidence of nosocomial infection. According to our results, prolongation of prophylaxis >48 h increases the infection rate.