Background: National Comprehensive Cancer Network recommends direct oral anticoagulants (DOACs) as preferred agents for treatment of cancer associated VTE in patients without gastric or gastroesophageal lesions. Currently at Massachusetts General hospital (MGH), DOACs are used in treatment of cancer associated VTE. This study was performed to evaluate the safety and efficacy of DOACs for treatment of VTE in patients with metastatic lung cancer. Methods: Retrospective chart review of patients at MGH with diagnosis of metastatic lung cancer who were prescribed edoxaban, rivaroxaban, or apixaban for treatment of VTE between January 2018 and January 2021 was performed. Patients were identified using electronic medical record reports. Data was collected on age, anticoagulation regimen, intent of anticoagulation therapy, presence of brain metastasis, renal function, liver function and platelet counts. The primary outcome was to assess the incidence of treatment failure, defined as VTE recurrence or major bleeding leading to a change in anticoagulation therapy. Results: 152 patients were evaluated, of which 57 received apixaban, 44 rivaroxaban, and 7 edoxaban. Most (n = 93) patients received enoxaparin for 14-90 days prior to transitioning to DOACs. Median age and creatinine clearance were 69 years and 63 mL/min, respectively. All patients had platelet count ≥ 50K/uL. Brain metastasis was present in n = 39 patients. Pulmonary embolism (PE)(n = 98), deep vein thrombosis (DVT) (n = 52), or both (n = 2) were the indication for DOAC therapy. Bleeding occurred in 14 patients including gastrointestinal bleeding (n = 5), hematuria (n = 4), epistaxis (n = 1), and hemoptysis (n = 4). Among patients with bleeding events, 7 received rivaroxaban and 7 received apixaban. Major recurrent VTE while on DOACs occurred in 5 of patients, including DVT (n = 2) and PE (n = 3). Patients with recurrent VTE received rivaroxaban (n = 7), apixaban (n = 3) and edoxaban (n = 1). All patient whom experienced bleeding and VTE were ≥ 60 years old. Brain metastasis was present in n = 2 of patients with bleeding events and n = 2 patients with recurrent VTE. Majority of patients (n = 93) received enoxaparin for 14-90 days prior to transitioning to DOACs. The median interval between initiation of DOACs and bleeding was 60 days (range 30-365) and recurrent VTE event was 90 days (range 60‐365). Conclusions: The results of this study suggest that outcomes of DOAC use for the treatment of cancer-associated VTE in patients with metastatic lung cancer are comparable to the results of large randomized controlled trials. DOAC therapy is a safe and effective anticoagulation option for lung cancer patients with cancer-associated thromboembolism.