Direct-acting oral anticoagulants (DOACs) have been introduced as alternatives to warfarin for stroke prevention in non-valvular atrial fibrillation and for treatment of venous thromboembolism. Many patients undergoing major gastrointestinal resections or bypass receive anticoagulants for various indications, including the treatment of thrombotic complication of surgery and prevention of visceral vessels events recurrence. DOACs have a wide therapeutic range that allows fixed dosing determined based on studies conducted in healthy subjects with normal absorptive capacity. Patients with significantly altered gastrointestinal tracts were not included in the Phase II and III studies that assessed DOAC efficacy and safety. The aim of this article is to review clinical data on DOACs use in patients with major surgical resection or bypass. MEDLINE and EMBASE were searched to identify studies and case reports of DOAC use in this population. Prescribing information for the four approved DOACs was also reviewed. The only types of available literature identified were case series and isolated case reports. Patients who underwent major distal intestinal resection were successfully anticoagulated with rivaroxaban, dabigatran was not effective. There is uncertainty about the efficacy of rivaroxaban and dabigatran in patients requiring anticoagulation after Roux-en-Y gastric bypass. Avoidance of rivaroxaban therapy in patients undergoing gastrectomy is advised Data are lacking regarding anticoagulation using apixaban and edoxaban in patients with major gastrointestinal resection or bypass is lacking. Clinicians should be aware of these limitations when using DOACs in this group of patients.