Comparative studies between different patient groups have suggested that cholecystectomy enhances bacterial dehydroxylation of the primary bile acid cholic acid (CA) to the secondary bile acid deoxycholic acid (DCA). DCA may exert a cocarcinogenic effect on the colonic mucosa. In a short-term follow-up study on nine female patients we found no alterations of the CA or DCA pools after cholecystectomy. However, in the long term, cholecystectomy could promote changes of the intestinal bacterial flora and thereby lead to enhanced conversion of CA to DCA, causing an expansion of the DCA pool size and a reduction of the CA pool size. To test this hypothesis, pool sizes, fractional turnover rates (FTR), and synthesis or input rates of CA, chenodeoxycholic acid (CDCA) and DCA were determined in 12 female patients before and again 5 to 8 years after cholecystectomy. In the long term, pool size and synthesis rate of CA had not changed and DCA pool size had expanded by only 7.5% (not significant [NS]). DCA input increased by 32% (NS) but was balanced by an increase in FTR of 36%. Pool size (-17%) and synthesis rate (-5%) of CDCA were not significantly diminished. Overall, the sizes of the total bile acid pool (-6%, NS; 50 5 8 vs. 53 -t 13 pmolkg) and the pool fractions of CA (44.7 -+ 10.3% vs. 42.8 5 7.6%) and DCA (25.5 -+ 14.1% vs. 23.6 t 9.3%) remained similar. In conclusion, cholecystectomy causes no changes in bile acid pool composition and thus has no adverse effects on bile acid metabolism in the long term. (HEPATOLOGY 1995;21:41-45.) Despite a variety of alternative therapeutic regimens cholecystectomy continues to be the gold standard for the treatment of cholesterol gallstone disease because laparoscopic cholecystectomy is minimally invasive Abbreviations: APE, atom percent excess; CA, cholic acid; CCK, cholecystokinin; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; FTR, fractional turnover rates; NS, not significant; R, 1sC/'2C isotope ratios; X, mean; ALT, alanine transaminase; AST, aspartate transaminase.