Schreuders EH, et al. - Through a population-based study of a random selection of asymptomatic people aged 50–74 years in the Rotterdam-Rijnmond region, the Netherlands between 2006 and 2015, the experts analyzed multiple rounds of one sample faecal immunochemical test (FIT) (1-FIT) with 2-FIT screening relative to participation, positive predictive value (PPV), diagnostic yield, and interval colorectal cancer. Out of a total of 10,008 people for the 1-FIT cohort, 9,787 were eligible for inclusion, of whom 7,310 were engaged at least once in four successive rounds and out of 3,197 invited individuals for the 2-FIT cohort, 3,131 were eligible for inclusion, and 2,269 were engaged in at least once in four successive rounds. Among participants who participated at least once, the cumulative positivity rate over four rounds for the 1-FIT cohort and for the 2-FIT cohort were 19·2% (1,407 of 7,310) and 28·5% (647 of 2,269), respectively. For advanced neoplasia, the cumulative PPV was 33·0% (432 of 1,308 colonoscopies) for the 1-FIT cohort vs 24·2% (147 of 607 colonoscopies) for the 2-FIT cohort. The cumulative diagnostic yield of advanced neoplasia among invited individuals was 4·4% (432 of 9,787) and 4·7% (147 of 3,131) for 1-FIT and for 2-FIT screening, respectively. In eight of 7,310 participants in the 1-FIT cohort and two of 2,269 with 2-FIT screening, FIT interval colorectal cancers were identified. Hence, in comparison with 1-FIT, 4 rounds of 2-FIT screening with a low fecal hemoglobin cutoff level could not lead to a notable rise in diagnostic yield or a decrease in interval colorectal cancers, regardless of the higher colonoscopy demand. Therefore, 1-FIT colorectal cancer screening programs should be favored.