Iatrogenic perforation of the gallbladder (PGB) during laparoscopic cholecystectomy (LC) leads to spillage of bile and gallstones into the peritoneal cavity, which can result in serious postoperative infection. The objective of this study is to prospectively evaluate with long-term follow-up the risk factors, mechanisms, and complications associated with PGB in patients undergoing LC. Data from 1412 patients undergoing LC were collected prospectively between 1989 and 1995. Patients with and without iatrogenic gallbladder perforation were compared. Long-term follow-up was obtained using mailed questionnaires and telephone interviews, when needed. Of the 1412 patients, 512 (36%) sustained a PGB. Male sex, weight, gallbladder inflammation, thickening of the gallbladder, presence of adhesions, and a difficult hilar dissection were all associated with an increased incidence of PGB. The most common mechanisms of PGB were laceration due to grasper traction (55%) and electrocautery dissection (40%). Both the operating time and length of hospital stay were significantly longer in the PGB group. No difference was observed in the rate of wound infections between PGB and non-PGB patients (1.6% versus 1.8%). Only one patient (with an inflamed and perforated gallbladder) developed an early postoperative intra-abdominal abscess. Long-term follow-up averaging 48 months was achieved with a response rate of 44 per cent. No late intra-abdominal abscesses or complications attributable to retained gallstones were discovered.