Reducing mortality from colorectal cancer (CRC) may be achieved by the introduction of population-based screening programs. The aim of the systematic review was to update previous research to determine whether screening for CRC using the fecal occult blood test (FOBT) reduces CRC mortality and to consider the benefits, harms, and potential consequences of screening. We searched eight electronic databases (Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, SIGLE, and HMIC). We identified nine articles describing four randomized controlled trials (RCTs) involving over 320,000 participants with follow-up ranging from 8 to 18 yr. The primary analyses used intention to screen and a secondary analysis adjusted for nonattendance. We calculated the relative risks and risk differences for each trial, and then overall, using fixed and random effects models. Combined results from the four eligible RCTs indicated that screening had a 16% reduction in the relative risk (RR) of CRC mortality (RR 0.84, 95% confidence interval [CI] 0.78-0.90). There was a 15% RR reduction (RR 0.85, 95% CI 0.78-0.92) in CRC mortality for studies that used biennial screening. When adjusted for screening attendance in the individual studies, there was a 25% RR reduction (RR 0.75, 95% CI 0.66-0.84) for those attending at least one round of screening using the FOBT. There was no difference in all-cause mortality (RR 1.00, 95% CI 0.99-1.02) or all-cause mortality excluding CRC (RR 1.01, 95% CI 1.00-1.03). The present review includes seven new publications and unpublished data concerning CRC screening using FOBT. This review confirms previous research demonstrating that FOBT screening reduces the risk of CRC mortality. The results also indicate that there is no difference in all-cause mortality between the screened and nonscreened populations.