Bacterial infection remains a major problem after solid organ transplantation (SOT), especially in children. Piperacillin-tazobactam (Pip-Tazo) is a beta-lactam-antibiotic combination with a broad spectrum of activity including gram-positive cocci as well as gram-negative rods, non-fermentative and anaerobic bacteria. The aim of this retrospective study was to critically review our experience with Pip-Tazo as perioperative prophylactic agent in pediatric non-renal SOT. Between 1993 and 2003 Pip-Tazo was used as initial perioperative prophylaxis in 45 pediatric patients who underwent a total of 49 transplants (36 liver-, seven cardiac-, two lung-, and four small bowel-) at our department. Median age of the children was 7.9 (range 0.5-18.1) years. A total of 34 rejection episodes following 27 transplants were diagnosed. During first hospitalization 44 infectious episodes were observed. Bacteria were responsible for 22 episodes including sepsis (n = 10), pneumonia (n = 5), wound infection (n = 4), urinary tract infection (n = 1), and clostridial colitis (n = 2). The isolated organisms were gram-positive cocci (n = 12), gram-negative rods (n = 3), non-fermentative bacilli (n = 4), and anaerobes (n = 3). Ten episodes were caused by Pip-Tazo resistant bacteria. Twenty-one of these infections were observed following antirejection therapy with pulse steroids. At later time points nine infectious episodes were successfully treated with a second course of Pip-Tazo. During follow up, eight patients died. Six deceased perioperatively: five from infection including aspergillosis (n = 4) and Pneumocystis jiroveci pneumonia (n = 1) and cerebrovascular bleeding (n = 1) and two children later on. At present 37 children (82%) are alive with well functioning graft after a median follow up of 39.2 (range 0.6-123.5) months. No severe side effects caused by Pip-Tazo were observed in any of the children. Pip-Tazo may be a suitable single agent for perioperative prophylaxis in pediatric non-renal solid organs recipients, however, a prospective comparative study is needed to make final conclusions.