Surgical site infections are common bacterial infections in orthotopic liver transplantation. The purpose of this study was to determine the incidence, timing, location, and risk factors, specifically antibiotic prophylaxis, for surgical site infections. A prospective study was performed that included a population of 1222 consecutive patients (73.0% males) who underwent liver transplantation in Spanish hospitals belonging to the Red de Estudio de la Infección en el Trasplante research network. One hundred seven patients developed surgical site infections. The predominant infection sites were incisional wound (53 episodes) and peritonitis (40 episodes). The timing of the organ/space surgical site infections was slightly delayed in comparison with incisional surgical site infections. Enterococcus spp., Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii were the predominant pathogens. Choledochojejunal or hepaticojejunal reconstruction (odds ratio, 4.2; 95% confidence interval, 1.6–10.7), previous liver or kidney transplant (odds ratio, 2.6; 95% confidence interval, 1.1–6.3), and more than 4 red blood cell units transfused (odds ratio, 2.0; 95% confidence interval, 1.1–3.4) were independently associated with the development of surgical site infections. Biliary reconstruction by choledochojejunostomy or hepaticojejunostomy increases the risk of surgical site infections. Liver Transpl 14:799–805, 2008. © 2008 AASLD.