Bladder cancer is a common urological malignancy with high recurrence rate, which may be reduced by chemoprevention. The aim was to evaluate chemoprevention in a mouse model of tobacco carcinogen-induced bladder tumors. A total of 60 A/J mice were randomized to normal diet, diet with low calcium, and diet with chemoprevention (acetyl salicylic acid, 1-alpha 25(0H)2-vitamin D3 and calcium). There were significantly fewer tumors (0 (0-0) vs. 0 (0-2), p = .045) and fewer animals with tumors (0/20 vs. 5/20, p = .045) in the chemoprevention group compared with controls. Thus, chemoprevention diet effectively reduced the tumor promoting effect of tobacco carcinogens in the mouse bladder.