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Background and aims Patients on parenteral nutrition for short bowel syndrome (SBS) have a high risk of thrombotic complications and are often treated with parenteral anticoagulation. Direct oral anticoagulants are absorbed proximally in the digestive tract and may represent alternative regimens in selected SBS patients. In our pilot study, we provided pharmacokinetics parameters of dabigatran etexilate and rivaroxaban in this setting and compared peak (Cmax), trough (Ctrough) concentrations, and areas-under-the-concentration-time-curve (AUC 0 − t ) to reference values retrieved from phase I-III studies. Methods We enrolled 6 adults with a remaining small bowel length ≤ 200 cm, normal renal/hepatic function, and intact stomach. In our crossover study, patients were exposed to twice-daily dabigatran etexilate 150 mg and once-daily rivaroxaban 20 mg. Results After 5 days of dabigatran dosing, Ctrough and Cmax geometric means were 39 μg/L (90% CI: 23–66) and 88 μg/L (90% CI: 56–137), respectively; AUC 0–12 h was 958 μg ∗ h/L (90% CI: 635–1445). After 5 days of rivaroxaban dosing, Ctrough and Cmax geometric means were 9 μg/L (90% CI: 1–71) and 167 μg/L (90% CI: 102–276), respectively; AUC 0–24 h was 1720 μg ∗ h/L (90% CI: 899–3300). Absorption was negligible in one patient with ultra-short (~ 15 cm) bowel. For dabigatran, Cmax ratio was 0.57 (SD 0.33) and Ctrough ratio was 0.35 (SD 0.44). For rivaroxaban, the mean observed-to-reference ratios AUC 0–24 h and Cmax ratios were 0.73 (SD 0.32) and 0.76 (SD 0.34), respectively. Conclusions While in SBS patients there is some absorption of the oral anticoagulants dabigatran etexilate and rivaroxaban, it appears to be lower than reference values. Plasma drug levels showed significant inter-individual variability. [ABSTRACT FROM AUTHOR]