PROJECT SUMMARY Background: Venous thromboembolism (VTE) is one of the most common causes of death in cancer patients. Guidelines recommend the use of VTE risk-stratification to identify ambulatory patients with cancer at high-risk of VTE who may benefit from primary VTE prevention with prophylactic anticoagulation. However, our preliminary data suggest that VTE risk assessment and primary prophylaxis are substantially underused. Aims and Methods: The overall objective of this project is to develop a feasible, effective, and sustainable implementation strategy to promote the uptake into clinical practice of evidence-based guidelines for VTE prevention in patients with cancer. The Specific Aims of this proposal are to: Aim 1: Conduct formative research to develop an implementation strategy (PREVenT-APC) promoting the uptake in clinical practice of a guideline-recommended, risk-based approach to primary VTE prevention for ambulatory patients with cancer; Aim 2: Using a randomized trial, assess effectiveness of the refined PREVenT-APC strategy as compared with usual care, to start and maintain thromboprophylaxis for identified high-risk patients with cancer; and Aim 3: Explore implementation outcomes and the contextual factors associated with variability in adoption, fidelity, effectiveness, and acceptability of the PREVenT-APC implementation strategy. To carry out the study, I will develop the PREVenT-APC strategy and conduct usability testing to refine the strategy (Aim 1); test the PREVenT-APC strategy via a randomized trial (Aim 2); and, using mixed methods, evaluate additional implementation outcomes, and explore variability in outcomes of the PREVenT-APC strategy (Aim 3). Career Development and Future Work: Through the objectives of the K23 Mentored Career Development Award, I will acquire advanced knowledge and apply skills in mixed method research, behavioral intervention clinical trial design, and dissemination and implementation science, which will further my goal of becoming an independent physician scientist with expertise in developing, implementing, and evaluating strategies to improve cross-specialty hematology care. The study findings will serve as a foundation for future R-level proposals to tailor and test adaptations and dissemination of the PREVenT-APC implementation strategy in different settings. Ultimately, the long-term goal of the proposed research is to reduce VTE and improve outcomes for patients with cancer.