The use of nonsteroidal anti‐inflammatory drugs has been suggested to have a chemopreventive effect against colon carcinoma, through the inhibition of cyclooxygenases 1 and 2, in patients with familial adenomatous polyposis and in animal models. Acarbose, an alpha‐glycosidase inhibitor, may also be chemopreventive. In order to examine the effects of these drugs we employed APC gene knockout mice randomized into 3 groups, one for treatment with piroxicam (0.05% concentration in drinking water), one for acarbose (0.04% concentration in food) and another for the control. After 14 weeks of treatment, mice were killed for quantitation of gastric and intestinal adenomas. Tumor multiplicity in the whole gastrointestinal tract decreased from 33.89±13.07 tumors/mouse in the control group to 17.05±7 tumors/mouse in the piroxicam‐treated group (P<0.001). The decrease in the acarbose‐treated group (29.68±12.86 tumors/mouse) was not significant (P>0.05). The number of tumors ≥3 mm in diameter was also quantified in all gastrointestinal segments. The number of such tumors in the piroxicam group was decreased to 0.56±1.2 tumors/mouse from the control value of 3.78±1.17 tumors/mouse (P<0.001), while in the acarbose‐treated group the number decreased to 2.36±1.7 tumors/mouse (P<0.01). Thus, piroxicam decreases the size and number of gastrointestinal adenomas in APC 1309 knockout mice, while acarbose decreases only the size.