- OBJECTIVE: To review novel oral anticoagulant (NOAC) trials in the treatment of venous thromboembolism (VTE) and the possible use of risk-stratification tools to guide their use in practice. SCOPE: MEDLINE and Cochrane databases were searched to identify relevant journal articles published from January 1982 to February 2013. Additional references were obtained from articles extracted during the database search. FINDINGS: NOACs have been developed to optimize VTE management and overcome the limitations of heparin and vitamin K antagonists (VKA). The AMPLIFY and EINSTEIN trials of apixaban and rivaroxaban, respectively, investigated single-drug management of VTE, whereas the edoxaban Hokusai-VTE trial and dabigatran RE-COVER and RE-COVER II trials investigated the use of NOACs with a heparin lead-in. The AMPLIFY and Hokusai-VTE trials are ongoing but the EINSTEIN and RE-COVER trials have demonstrated that rivaroxaban and dabigatran, respectively, are non-inferior to parenteral anticoagulants and warfarin in the management of VTE. Differences in study design complicate the application of study results to clinical practice. There are multiple validated DVT protocols that effectively and safely treat patients in outpatient settings. The pulmonary embolism (PE) severity index (PESI), simplified PESI (sPESI), and other prognostic tools have been used to risk stratify patients with PE by estimating mortality risk to guide outpatient eligibility. CONCLUSIONS: NOACs provide physicians with new therapeutic options in the management of VTE. While heparin and VKAs compose the current standard treatment for VTE, their use will likely disappear as physicians grow comfortable with the adoption of NOACs. As studies have not clearly defined the efficacy of these agents in certain patient populations, further data in special patient populations and risk stratification through the use of VTE severity scores could potentially be adapted to guide anticoagulant management and outpatient treatment eligibility.