BACKGROUND: Clinicians confront numerous practical issues in optimizing the use of anticoagulants to treat venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in their decisions about the use of anticoagulants in the management of VTE. These guidelines assume the choice of anticoagulant has already been made. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 25 recommendations and 2 good practice statements to optimize management of patients receiving anticoagulants. CONCLUSIONS: Strong recommendations included using patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy and against using periprocedural low-molecular-weight heparin (LMWH) bridging therapy. Conditional recommendations included basing treatment dosing of LMWH on actual body weight, not using anti-factor Xa monitoring to guide LMWH dosing, using specialized anticoagulation management services, and resuming anticoagulation after episodes of life-threatening bleeding.