Screening using the fecal occult blood test (FOBT) has been shown to reduce mortality from colorectal cancer. However, the impact of repeated screening on the detection of colorectal cancer and on false-negative results is unclear. Thus, we conducted a case-control study. Male patients with colorectal cancer, adenoma with high-grade dysplasia (polyp cancer) or adenomatous polyps, detected through screening using the FOBT between January 1996 and December 2007, were identified and their screening history was obtained. Patients with interval cancer, diagnosed within 1 year of the most recent FOBT, were also included. We identified 27 patients with interval cancer, 156 with colorectal cancer, 266 with polyp cancer, and 3566 with adenomatous polyps. Three controls for each patient with colorectal or interval cancer were selected randomly from patients with adenomatous polyp and polyp cancer, matched by diagnosis year and birth year. Odds ratios (ORs) for the diagnosis of colorectal cancer or interval cancer were estimated based on the frequency of screening. There was no apparent difference in the frequency of screening between the patients with colorectal cancer and the controls (polyp cancer and patients with adenomatous polyp). The OR (95% confidence interval) for being diagnosed with interval cancer after three or more screenings compared with a single screening was 0.07 (0.02-0.32), and the OR was 0.18 (0.05-0.66) compared with two screenings. The results of this study showed that repeated screening reduces the risk of being diagnosed with interval cancer.