Our objective was to compare the effectiveness of percutaneous cholecystostomy (PC) vs conservative treatment (CO) in high-risk patients with acute cholecystitis. The study was randomized and comprised 123 high-risk patients with acute cholecystitis. All patients fulfilled the ultrasonographic criteria of acute inflammation and had an APACHE II score > or =12. Percutaneous cholecystostomy guided by US or CT was successful in 60 of 63 patients (95.2%) who comprised the PC group. Sixty patients were conservatively treated (CO group). One patient died after unsuccessful PC (1.6%). Resolution of symptoms occurred in 54 of 63 patients (86%). Eleven patients (17.5%) died either of ongoing sepsis (n=6) or severe underlying disease (n=5) within 30 days. Seven patients (11%) were operated on because of persisting symptoms (n=3), catheter dislodgment (n=3), or unsuccessful PC (n=1). Cholecystolithotripsy was performed in 5 patients (8%). Elective surgery was performed in 9 cases (14%). No further treatment was needed in 32 patients (51%). In the CO group, 52 patients (87%) fully recovered and 8 patients (13%) died of ongoing sepsis within 30 days. All successfully treated patients showed clinical improvement during the first 3 days of treatment. Percutaneous cholecystostomy in high-risk patients with acute cholecystitis did not decrease mortality in relation to conservative treatment. Percutaneous cholecystostomy might be suggested to patients not presenting clinical improvement following 3 days of conservative treatment, to critically ill intensive care unit patients, or to candidates for percutaneous cholecystolithotripsy.