Abstract Objective To look for outcomes of patients (pts) with major gastrointestinal haemorrhage (mGIH) and ongoing anticoagulants out of four-year survey of community hospital with catchment area 197,722 inhabitants, of whom 15,267 with Warfarin (W) and 10,397 with direct oral anticoagulants (DOACs). DOACs were available for prescription in the catchment area since 4 years (dabigatran and rivaroxaban), 3 years (apixaban), and 2 years (edoxaban). Methods Haemorrhage (n=1,919) were submitted to propensity score matching for major bleeding; mGIH were enrolled and stratified according to ongoing W or DOACs. Primary endpoint was one-month death. Results Out of 476 mGIH, 73 pts received anticoagulants; 22 DOACs and 51 W; p=0.0006. Of note mGIH on W accounted for 2.7% (51/1,919) per year of pts, and 0.08% (51/15,267) of the catchment area. Conversely, mGIH on DOACs accounted as follows: dabigatran (n=10/476) 0.53%, rivaroxaban (n=6/476) 0.32%, apixaban (n=5/476) 0.35%, and edoxaban (n=1/476) 0.11% per year of pts; p=0.117. Rate of mGIH and DOACs versus (vs) rate of mGIH and W as follows: less than (−) 5 fold (2.7x100/0.53) of dabigatran vs W, p=0.004; −8 fold (2.7x100/0.32) of rivaroxaban vs W, p=0.0002; −7 fold (2.7x100/0.35) of apixaban vs W; p=0.ehz745.10188, and −25 fold (2.7x100/0.11) of edoxaban vs W; p=0.ehz745.101801. However no difference versus the catchment area per year (0.723): 0.07% (10/3,373) dabigatran, 0.04% (6/4,046) rivaroxaban, 0.08% (5/2,141) apixaban, 0.06% (1/839) edoxaban. Overall, one-month death accounted for 10/476 (2.1%). Of note 236 mGI were from the upper tract and 240 from the lower tract. Among upper tract, 10 pts received DOACs (4 dabigatran, 4 rivaroxaban, 2 apixaban, and 0 edoxaban) and 21 received W. One-month death was 0/10 DOACs versus 1/21 W, p=0.483. Among lower tract, 12 pts received DOACs (6 dabigatran, 2 rivaroxaban, 3 apixaban, and 1 edoxaban) and 30 pts received W; one-month death was 0 for every groop. Anticoagulant reversal treatment was given to 6/22 (27%) pts with DOACs versus 18/51 (35%) with W, p=0.014; transfusion to 6/22 (27%) versus 11/51 (22%), respectively, p=0.306; admission 19/22 (86%) versus 42/51 (82%), respectively, p=0.004. Sensitivity/specificity ratio of variables and biomarkers for aggressive pharmacological approach were obtained by area under ROC curve (AUC) >0.50. PTT value >37 sec (AUC 0.57) showed sensitivity 15%, specificity 90%; INR value >1.4 (0.50), sens 15%, spec 80%. In addition, warfarin (0.49) sens 15%, spec 80%; age ≥75 years (0.48) sen 60%, spec 40%. Gastrointestinal bleeding: flow-chart. Conclusion Out of four-year survey, pts with ongoing DOACs were less likely to have mGIH when compared to W. Patients with W were more likely to receive reversal tratment; pts with DOACs were more likely to undergo admission. Short-term mortality of pts with W was higher than DOACs. Aggressive pharmacological approach should be driven by PTT, INR, ongoing warfarin, and older age.