The results of 18 months mouse and 24 months rat carcinogenicity studies with the oral direct thrombin inhibitor ximelagatran are presented. In the mouse, gavage doses of ximelagatran up to 180 μmol/kg per d produced no neoplastic changes in any of the tissues examined. In the rat, gavage doses up to 240 μmol/kg per d produced multiple macroscopically detectable nodules in the pancreas, which are seen to be focal/multifocal acinar cell hyperplasia and focal/multifocal acinar cell adenoma upon histological evaluation. There were no other treatment-related effects on tumor incidence or distribution in the rat. The studies show a clear species difference in pancreatic effects between the rat and the mouse to long-term treatment with ximelagatran.