The severity of the bleeding, presence of ongoing bleeding risk factors, and elapsed time since the bleeding episode were also felt to influence the acceptability of the intervention. Conclusions and research needs for this recommendation. The guideline panel determined that there is uncertainty regarding the net health benefit from resuming anticoagulation therapy after surviving a major bleeding episode. Although only very low certainty evidence is available, some panel members felt that the potential to avoid mortality was more important than increasing the risk of recurrent bleeding. This recommendation specifically applies to patients who require long-term or indefinite anticoagulation (ie, are at moderate to high risk for recurrent VTE, are not at high risk for recurrent bleeding, and are willing to continue anticoagulation therapy). The available evidence was insufficient to allow the panel to state with certainty the optimal timing of anticoagulation therapy resumption. However, the panel determined that waiting at least 2 weeks but not more than 90 days after the bleeding event is reasonable based on the intervals for restarting anticoagulation therapy examined in clinical studies and depending on the patient-specific risk factors for thrombosis and bleeding (eg, indication for anticoagulation therapy and type of bleeding event). Earlier resumption may be appropriate if the source of bleeding is identified and corrected. The panel identified the following additional research questions. (1) What is the optimal timing of and what patient-specific factors should influence anticoagulation therapy resumption? (2) For patients who developed major bleeding during oral anticoagulant therapy, how does transition to an alternative anticoagulant influence the risk of bleeding recurrence? (3) What is the impact on mortality, recurrent VTE risk, and recurrent bleeding risk associated with resumption of anticoagulation therapy following extracranial bleeding from sites other than the gastrointestinal tract? 