OBJECTIVES: Sigmoidoscopy screening and fecal occult blood (FOB) tests have been demonstrated as effective ways to reduce mortality from colorectal cancer. However, most studies of colorectal cancer screening and cancer mortality have not taken into consideration lifestyle factors that could account for the observed associations. The purpose of this study was to determine the association between screening and incidence of colon cancer, taking into consideration important lifestyle factors. METHODS: We estimated the association between screening and colon cancer after taking into consideration health and lifestyle factors using data obtained as part of population-based case-control study of incident colon cancers. RESULTS: Sigmoidoscopy screening, especially as part of a checkup, was protective against incident colon cancer in both men (OR 0.56, 95% CI 0.44-0.77) and women (OR 0.53, 95% CI 0.33-0.77) after adjusting for other risk factors for colon cancer. For men, associations were stronger for distal tumors (OR 0.48, 95% CI 0.31-0.71) than for proximal tumors (OR 0.67, 95% CI 0.45-1.11). We did not observe significant associations between FOB test and colon cancer. Differences in characteristics between those who were screened and not screened were also observed. Men were more likely to report having a sigmoidoscopy as part of a checkup than were women, as were people with higher levels of education. People who reported having a sigmoidoscopy as part of a checkup also reported eating diets lower in fat and higher in fiber, folate, and vegetables. Men were more likely to report higher levels of physical activity, and women were more likely to report taking hormone replacement therapy (HRT) if they also reported a sigmoidoscopy. Both men and women who reported a sigmoidoscopy for screening purposes were more likely to have a family history of colorectal cancer. CONCLUSIONS: These data provide additional support for the benefits of having a screening sigmoidoscopy. The associations between screening sigmoidoscopy and colon cancer do not appear to be the result of lifestyle factors.