Recent studies have shown telomere length shortening in colorectal carcinoma (CRC). However, to date, no prospective, epidemiologic data are available on examining mean leukocyte telomere length as a risk predictor. Using leukocyte DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we examined the relationship of mean telomere repeat copy number to single gene copy number (T/S ratio), using a modified quantitative PCR protocol, among 191 incident CRC cases (all white males), matched to 306 controls by age, smoking status, and length of follow-up. An inverse correlation between T/S ratio and age was observed in our sample population (P = 0.038). However, the T/S ratios were similar between cases and controls (P = 0.650). Furthermore, in a multivariable adjusted analysis, we found no evidence for an association of the observed T/S ratios with CRC risk (adjusted odds ratio, 1.249; 95% confidence interval, 0.863-1.808; P = 0.238). In summary, the present investigation found no evidence for an association of leukocyte mean telomere length with risk of incident CRC and further suggests that leukocyte mean telomere length may not be a useful indicator for risk assessment.