Several small series have suggested the efficacy of thrombolysis in patients with cerebral vein thrombosis (CVT). However, since no randomised controlled trials have compared the use of thrombolysis with anticoagulant treatment in these patients, the risk to benefit ratio of this approach remains uncertain. The aim of this study is therefore to assess the safety of thrombolysis in CVT estimating mortality and major bleeding complications. MEDLINE and EMBASE databases were searched up to June 2010. Two reviewers performed study selection independently. Studies providing data on mortality and/or on the incidence of major bleeding complications were potentially eligible for the study. Two reviewers independently extracted data on study and population characteristics, type, dose and administration route of thrombolytic treatment; use and dose of concomitant heparin. Weighted mean proportion of the mortality rate and of the rate of major and non-major bleeding complications were calculated. Fifteen studies for a total of 156 patients were included. Twelve patients died after thrombolysis (weighted mean 9.2%; 95% CI 4.3, 15.7%) and 15 patients had a major bleeding complication (weighted mean 9.8%; 95% CI 5.3, 15.6%). Twelve haemorrhages were intracranial (weighted mean 7.6%; 95% CI 3.5, 13.1%), and seven of these patients died (58.3%; 95% CI 32.0, 80.7%). Our results suggest that thrombolysis is associated with a nonnegligible incidence of major bleeding complications, including intracranial bleeding potentially affecting patients outcome. Future studies are necessary to evaluate the safety of thrombolysis in comparison to more conservative strategies.