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The objective of this study was to study predictors of patients' participation in colorectal cancer (CRC) screening.Men and women, aged 55–64 years, were randomized to the following: (i) biennial fecal occult blood test (FOBT) delivered by mail (n=2,266); (ii) FOBT delivered by a general practitioner (GP)/screening facility (n=5,893); (iii) “once-only” sigmoidoscopy (FS) (n=3,650); (iv) FS followed by FOBT for screenees with negative FS (n=10,867); and (v) patient's choice between FS and FOBT (n=3,579). A stratified (by screening arm) random sample of attenders and nonattenders was contacted by trained interviewers 4 months after the initial invitation. Subjects giving their consent were administered a questionnaire (available online) investigating perceptions of individual CRC risk, attitudes toward prevention, adoption of health protective behaviors, and reasons for attendance/nonattendance. Adjusted prevalence odds ratios (ORs) were computed by multivariable logistic regression.The response rate was 71.9% (701 of 975) among nonattenders and 88.9% (773 of 870) among attenders. Adjusting for screening arm, center, gender, age, and education, participation was significantly higher among people who consulted their GP before undergoing screening (OR: 4.24; 95% confidence interval (CI): 3.11–5.78), who mentioned one first-degree relative with CRC (OR: 3.62; 95% CI: 2.02–6.49), who reported regular physical activity (OR: 1.85; 95% CI: 1.33–2.55), and who read the mailed information (letter only: OR: 1.85; 95% CI: 1.23–2.78; letter+leaflet: OR: 3.18; 95% CI: 2.12–4.76). People who considered screening to be ineffective (OR: 0.12; 95% CI: 0.08–0.19), those who considered it to be effective but reported even moderate levels of anxiety (OR: 0.32; 95% CI: 0.23–0.45), and those who mentioned previous knowledge of CRC screening tests were less likely to accept the invitation (OR: 0.49; 95% CI: 0.34–0.70).Adoption of health protective behaviors is associated with a higher attendance rate, whereas anxiety represents a strong barrier, even among people who deemed screening to be effective. Increasing the proportion of people who consult their GP when making a decision regarding screening might enhance participation.