Whether it is necessary to perform biliary drainage for obstructive jaundice before performing pancreaticoduodenectomy remains controversial. Our aim was to determine the impact of preoperative biliary drainage on intraoperative bile cultures and postoperative infectious morbidity and mortality following pancreaticoduodenectomy. We retrospectively analyzed 161 consecutive patients undergoing pancreaticoduodenectomy in whom intraoperative bile cultures were performed. Microorganisms were isolated from 58% of these intraoperative bile cultures, with 70% of them being polymicrobial. Postoperative morbidity was 47% and mortality was 5%. Postoperative infectious complications occurred in 29%, most commonly wound infection (14%) and intra-abdominal abscess (12%). Eighty-nine percent of patients with intra-abdominal abscess (P = 0.003) and 87% with wound infection (P = 0.003) had positive intraoperative bile cultures. Microorganisms in the bile were predictive of microorganisms in intraabdominal abscess (100%) and wound infection (69%). Multivariate analysis of preoperative and intraoperative variables demonstrated that preoperative biliary drainage was associated with positive intraoperative bile cultures (P <0.001), postoperative infectious complications (P = 0.022), intra-abdominal abscess (P = 0.061), wound infection (P = 0.045), and death (P = 0. 021). Preoperative biliary drainage increases the risk of positive intraoperative bile cultures, postoperative infectious morbidity, and death. Positive intraoperative bile cultures are associated with postoperative infectious complications and have similar microorganism profiles. These data suggest that preoperative biliary drainage should be avoided in candidates for pancreaticoduodenectomy.