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Fecal immunochemical tests (FITs) are recommended to screen average-risk adults for colorectal cancer (CRC). Little research has examined whether a two-sample FIT affects participant uptake, compared with a one-sample FIT. Examining participant uptake is important, as evidence suggests that a two-sample FIT may increase the sensitivity to detect CRC.This study had two objectives: (i) to evaluate FIT completion in a population that received either a one-sample FIT kit (1-FIT) or a two-sample FIT kit (2-FIT) and (ii) to understand whether uptake varies by age, sex, or receipt of prior CRC screening.We conducted a randomized controlled trial in which 3081 participants who were aged between 50 and 75 years and were at an average risk for CRC, and who had requested FITs, randomly received 1-FIT (n=1540) or 2-FIT (n=1541) kits. FIT completion was defined as the completion and return of a one-sample test by the patients in the 1-FIT group or of both sample tests by those in the 2-FIT group. Cox proportional hazard regression models were used to determine the independent effect of group type (2-FIT vs. 1-FIT) on the completion of the FIT, adjusting for age, sex, and receipt of prior CRC screening.The 2-FIT group had lower test completion rates (hazard ratio=0.87; 95% confidence interval=0.78–0.97; P=0.01) after adjusting for age, sex, and receipt of prior CRC screening. Participant uptake did not vary by age, sex, or receipt of prior CRC screening.This unique, rigorous randomized controlled trial found that the 2-FIT regimen decreases completion of FIT. Further research is needed to understand whether decreases in participant uptake are offset by increased gains in test sensitivity.