Introduction: Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT. Methods: We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology. Results: Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I 2 =0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I 2 =0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I 2 =0%; 9 studies). Conclusions: Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.