ObjectivesCurrent guidelines do not recommend direct oral anticoagulants (DOACs) to treat cerebral venous thrombosis (CVT) despite their benefits over standard therapy. We performed a systematic review to summarise the published experience of DOAC therapy in CVT.Data sourcesMEDLINE, Embase and COCHRANE databases up to 18 November 2020.Eligibility criteriaAll published articles of patients with CVT treated with DOAC were included. Studies without follow-up information were excluded.Data extraction and synthesisTwo independent reviewers screened articles and extracted data. A risk of bias analysis was performed.Primary and secondary outcome measuresSafety data included mortality, intracranial haemorrhage (ICH) or other adverse events. Efficacy data included recurrent CVT, recanalisation rates and disability by modified Rankin Scales (mRS).Results33 studies met inclusion criteria. One randomised controlled trial, 5 observational cohorts and 27 case series or studies reported 279 patients treated with DOAC for CVT: 41% dabigatran, 47% rivaroxaban, 10% apixaban and 2% edoxaban, in addition to 315 patients treated with standard therapy. The observational cohorts showed a similar risk of death in DOAC and standard therapy arms (RR 2.12, 95% CI 0.29 to 15.59). New ICH was reported in 2 (0.7%) DOAC-treated patients and recurrent CVT occurred in 4 (1.5%). A favourable mRS between 0 and 2 was reported in 94% of DOAC-treated patients, more likely than standard therapy in observational cohorts (RR 1.13, 95% CI 1.02 to 1.25).ConclusionThe evidence for DOAC use in CVT is limited although suggests sufficient safety and efficacy despite variability in timing and dose of treatment. This systematic review highlights that further rigorous trials are needed to validate these findings and to determine optimal treatment regimens.