For the comparison of each of the NOACs with VKA in the initial and long-term treatment of VTE, current evidence for ef cacy is moderate or high quality, for safety (risk of bleeding) is moderate or high quality, and overall is moderate or high quality (Tables 2-5, e-Tables 5-8). In the 10th Edition of the Antithrombotic Guideline (AT10), the panel s overall assessment of the relative ef cacy and risk of bleeding with different anticoagulant agents is that: (1) the risk reduction for recurrent VTE with all of the NOACs appears to be similar to the risk reduction with VKA,35 including in patients with ; (2) in patients with VTE and cancer, the risk reduction for recurrent VTE appears to be greater with LMWH than with VKA therapy1,36,40 ; (3) the risk reduction for recurrent VTE with the NOACs compared to LMWH has not been assessed but, based on indirect comparisons, LMWH may be more effective that the NOACs in patients with VTE and cancer36 ; (4) the risk reduction for recurrent VTE with different NOACs has not been directly compared but, based on indirect comparisons, appears to be similar to all of the NOACs35 ; (5) the risk of bleeding with the NOACs, and particularly intracranial bleeding, is less with the NOACs than with ; (6) based on patients with atrial brillation, GI bleeding may be higher with dabigatran, rivaroxaban, and edoxaban than with VKA therapy, although this has not been seen in patients with ; (7) based on indirect comparisons, the risk of bleeding may be lower with apixaban than with the ; and (8) despite the lack of speci c reversal agents for the NOACs, the risk that a major bleed will be fatal appears to be no higher for the NOACs than for VKA therapy.33,34,45 Based on less bleeding with NOACs and greater convenience for patients and health- care providers, we now suggest that a NOAC is used in preference to VKA for the initial and long-term treatment of VTE in patients without cancer. 