Our study investigated the risks of genotypes of N-acetyltransferase 2 (NAT2), tobacco use and/or occupational exposure to carcinogens in patients with bladder cancer and in age- and sex-matched controls in Japanese. NAT2 genotypes were categorized into two groups, homozygous mutant (slow acetylator genotype) and homozygous and heterozygous wild type (fast acetylator genotype). The percentage of NAT2 slow acetylator types was 6.7% in the bladder cancer patients, close to the value for controls (6.1%). There was no association between NAT2 slow acetylator genotype and the risk of bladder cancer. This association was also insignificant when subjects were restricted to those who used tobacco or those occupationally exposed to carcinogens. In contrast, tobacco use in combination with exposure to carcinogens was a significant risk factor, as based on the odds ratio and chi-square test. The combination of both factors should be an additive risk factor for bladder cancer. In this study, we demonstrated that the environmental factors of smoking habit and occupational exposure for carcinogenicity are much more important than genetic factors in bladder cancer.