Screening sigmoidoscopy is associated with a reduction in both the incidence and mortality of colorectal cancer. Although current guidelines recommend sigmoidoscopy screening every 5 years, the duration of risk reduction is not known. We conducted a population-based case-control study to examine the association between sigmoidoscopy screening and colorectal cancer incidence. We collected information on screening history and risk factors from case patients with distal (n = 1026) and proximal (n = 642) colorectal cancer and from 1294 control subjects from October 1998 through February 2002. Screening sigmoidoscopy was associated with a statistically significant reduction in the incidence of distal colorectal cancer (odds ratio [OR] = 0.24, 95% confidence interval [CI] = 0.17 to 0.33). These reductions were sustained for up to 16 years with little attenuation. We also observed strong inverse associations between cancer incidence and sigmoidoscopy in analyses that included subjects with symptom-related tests. Current recommendations regarding the frequency of sigmoidoscopy screening may be unnecessarily aggressive.