Background Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic treatment on the FIT-based Danish national screening program for CRC.

Methods This was a cross-sectional study of all individuals returning a FIT from 2014 until 2016. The effect of antithrombotic treatment on FIT positivity and the positive predictive value (PPV) were assessed using proportions and multivariable Poisson regression.

Results Of 884 036 invited individuals, we identified 551 570 participants. A positive FIT was observed in 9052 of 77 007 individuals (11.8 %) receiving antithrombotic treatment compared with 28 387 of 474 587 individuals (6.0 %) receiving no treatment. The adjusted relative risk (RR) for a positive FIT was 1.59 (95 %CI 1.56–1.63) for any treatment. Nonvitamin K oral anticoagulants (NOACs) were associated with the largest increase in FIT positivity (adjusted RR 2.40, 95 %CI 2.48–2.54). The proportion of CRC detected at colonoscopy was slightly lower among patients on antithrombotic treatment (6.0 %, 95 %CI 5.5 %–6.6 %) than among treatment-naïve patients (6.4 %, 95 %CI 6.1 %–6.7 %). The PPV for CRC or high risk adenomas was decreased nearly twofold in patients treated with NOAC (adjusted RR 0.58, 95 %CI 0.51–0.66]).

Conclusion Antithrombotic treatment was associated with a decreased PPV in FIT-based CRC screening