Background: Prophylactic antibiotic therapy is given routinely in the peri-operative period to prevent surgical site infection. However, in pediatric cardiac surgery, an optimal schedule has not been defined. Pediatric recommendations follow the guidelines for adults, which might be improper because of the inherent challenges in pediatric research and the heterogeneity of the population. Implementation of an effective prophylaxis protocol is needed for children undergoing cardiac surgery, especially in view of worldwide antibiotic overuse and the development of drug resistance. In this review, we analyze the current knowledge supported by up-todate publications about antibiotic prophylaxis in pediatric cardiac surgery. Methods: The PubMed Ò database was searched for full-text journal articles describing peri-operative antibiotic prophylaxis in pediatric cardiac surgery published since 2000. Antibiotics used for standard prophylaxis with dosing schema, time of the first dose, additional dosage in extracorporeal circulation (ECC) priming, and prophylaxis duration were analyzed. Additionally, we looked for special clinical situations such as antibiotic prophylaxis in children with the sternum left open after surgery and patients with b-lactam allergy or preoperative methicillin-resistant Staphylococcus aureus (MRSA) colonization or those requiring extracorporeal membrane oxygenation (ECMO). Results: A total of 1,546 articles were evaluated, and we identified 20 for further analysis. On the basis of the current peri-operative antibiotic prophylaxis recommendations for cardiac surgery and the papers reviewed, we tried to propose a schedule for peri-operative antibiotic prophylaxis in pediatric cardiac surgery. Conclusions: There is a need for careful use and examination of the schedule proposed because the pharmacokinetics of antibiotics in pediatric patients with ECC is not fully understood. This should be evaluated further. Formulating uniform recommendations concerning peri-operative antibiotic prophylaxis is difficult.