Background: Bladder cancer (BC) screening is not accepted in part due to low overall incidence. We utilized the PLCO and NLST to identify optimal high-risk populations most likely benefit from screening. Methods: Data were extracted from PLCO and NLST to stratify risk of BC by overall population, gender, race, age at inclusion and smoking status. Incidence rates between groups were compared using chi-square test. Results: BC was identified in 1430/154,898 in PLCO and 439/53,173 in NLST. BCs were grades III/IV in 36.8% and 41.3%, respectively. Incidence rates were significantly higher in men than women (PLCO: 1.4 vs. 0.31/1000 person-years, NLST: 1.84 vs. 0.6/1000 person-years, both p<0.0001). In proportional hazards models, male sex, higher age, duration and intensity of smoking were associated with higher risk of BC (all p<0.0001). In men >70 with smoking exposure of 30 pack years (PY) and more, incidence rates were as high as 11.92 (PLCO) and 5.23 (NLST) (per 1000 person-years). In current high intensity smokers (≥50 PY) the gender disparity in incidence persists in both trials (0.78 vs. 2.99 per 1000 person-years in PLCO and 1.12 vs. 2.65 per 1000 person years in NLST). Conclusions: Men over 60 years with a smoking history of >30 PY generate incidence rates over 2/1000 person-years, which could serve as an excellent population for screening trials. Gender differences in BC incidence cannot be readily explained by differences in exposure to tobacco, since in PLCO and NLST the gender disparity persisted regardless of smoking intensity.