Background: Acute septic cholecystitis (AC) remains a difficult problem in patients with coexisting severe illness, and ultrasonographically guided percutaneous puncture and drainage of the gallbladder (PTBD) may be an alternative treatment in this context. Setting: University Hospital, Norway. Methods: Retrospective study of the safety and efficacy of this approach in 86 consecutive patients treated from 1992 to 1999. Results: Five patients died. Drainage did not seem to influence the condition in these patients, who were drained for a mean of 8 days after admission compared to 4 days for the survivors (p = 0.01), and had a higher S-bilirubin on the day of the drainage, 46 and 29 µmol/l (p = 0.05), respectively. Seven patients had an intraperitoneal bile leak and 2 had worsening septicemia. One of these patients had both, and the gallbladder was removed. An open cystic duct demonstrated at catheter cholangiography was associated with a bile leak in 3 (4%) of 76 patients as opposed to 4 (40%) of 10 patients with obstruction (p = 0.001). Only 60 patients survived another 6 months because of general debility and other diseases. Twenty-seven (45%) of these were asymptomatic during follow-up. Twenty-eight (47%) of the remaining patients had at least one recurrent episode of AC. One patient who was readmitted due to AC had urgent cholecystectomy and 8 others had elective cholecystectomy during follow-up for a total cholecystectomy rate of 12%. A common bile duct stone was demonstrated in 4 patients after ERCP and indicative signs were found in another 5 (10%). Conclusions: PTBD remains a good option in patients with septic AC who have severe coexisting disease and may be too ill to undergo an operation. It may not be necessary to remove the gallbladder in 45% or more of the patients as many remain asymptomatic after PTBD.