PURPOSE We investigated whether the polymorphisms of N-acetyltransferase 2 (NAT2), glutathione S-transferase-mu (GSTM1) and glutathione S-transferase-theta (GSTT1) genes were risk factors of bladder cancer among Korean people in relation to other risk factors. MATERIALS AND METHODS In this case-control investigation of 113 patients with primary bladder cancer and 221 control subjects, we compared the association of bladder cancer with genetic polymorphisms of NAT2, GSTM1 and GSTT1, demographic characteristics, smoking status, and medical histories in a molecular epidemiological way. RESULTS The risk of bladder cancer was significantly increased in patients with a medical history of tuberculosis (OR 3.61, 95% CI 1.57 to 8.26) and bronchial asthma (OR 4.15, 95% CI 1.61 to 10.75), while smoking history turned out to be insignificant. GSTM1 null genotype was a significant risk factor of bladder cancer (OR 1.81, 95% CI 1.12 to 2.93). On the other hand, slow acetylator and GSTT1 genotypes were insignificant. Also, we could not find any association between GSTM1, GSTT1, slow acetylator genotypes and bladder cancer risk among smokers. The rapid acetylator, GSTM1 null and GSTT1 null genotypes with a medical history of asthma or tuberculosis combinations were significant risk factors in Korean subjects. CONCLUSIONS Among Korean subjects, GSTM1 null genotype was a significant risk factor for bladder cancer. The reason why bronchial asthma and tuberculosis are risk factors in Korean subjects is yet unknown, but a variety of factors, including enzyme activities for detoxification, medication for these diseases and immunological background might be involved.