Physical activity has been inconsistently associated with rectal cancer despite the consistent association between physical activity and colon cancer. In this study, the authors evaluated the association between physical activity and rectal cancer using the same questionnaire used to evaluate the previously reported association with colon cancer. A population-based study of 952 incident cases of cancer in the rectum and rectosigmoid junction and 1,205 age- and sex-matched controls was conducted in Utah and northern California at the Kaiser Permanente Medical Care Program between 1997 and 2002. Vigorous physical activity was associated with reduced risk of rectal cancer in both men and women (odds ratio (OR) = 0.60, 95% confidence interval (CI): 0.44, 0.81 for men; OR = 0.59, 95% CI: 0.40, 0.86 for women). Among men, moderate levels of physical activity also were associated with reduced risk of rectal cancer (OR = 0.70, 95% CI: 0.51, 0.97). Participation in vigorous activity over the past 20 years conferred the greatest protection for both men and women (OR = 0.55, 95% CI: 0.39, 0.78 for men; OR = 0.44, 95% CI: 0.30, 0.67 for women). In summary, physical activity was associated with reduced risk of rectal cancer in these data. The reduced risk was similar to that previously observed for colon cancer.