Although new oral anticoagulants (NOAs) have been marketed in many countries, concern exists about the management of bleedings related to these drugs due to the lack of specific antidotes. The aim of our study was to report on real life management of NOAs-related life-threatening or major bleedings. We report data from consecutive cases of NOAs related major bleedings admitted to 4 hospitals since NOAs became marketed in Italy. We treated 8 patients, 4 males, with mean age 84 ± 7 years, 7 of whom were on dabigatran and one on rivaroxaban. The indication for NOA was atrial fibrillation. All bleedings were spontaneous and involving the gastro-intestinal tract. At the time of bleeding all patients had a drop in hemoglobin levels over 20 g/L. Creatinine clearance was ≤30 mL/min in 4 patients. All patients received general supportive measures, 4 of 8 patients were transfused with packed red cells and one patient received platelet transfusion. Three patients were treated with tranexamic acid and one patient on dabigatran received 4-factor prothrombin complex concentrate (PCC) with bleeding cessation, although coagulation parameters were not corrected. The median time for normalization of coagulation parameters was 3 days (range 1-6 days). All patients were discharged alive and NOAs were discontinued. In NOAs related major gastro-intestinal bleeding general supportive measures seem to be effective for the majority of patients. Despite promoting bleeding cessation, 4-factor PCC does not reverse abnormal coagulation parameters.