The natural history and long-term prognosis of cerebral vein and dural sinus thrombosis (CVT) have not been examined previously by adequately powered prospective studies. We performed a multinational (21 countries), multicenter (89 centers), prospective observational study. Patients were followed up at 6 months and yearly thereafter. Primary outcome was death or dependence as assessed by modified Rankin Scale (mRS) score >2 at the end of follow-up. From May 1998 to May 2001, 624 adult patients with CVT were registered. At the end of follow-up (median 16 months), 356 patients (57.1%) had no symptom or signs (mRS=0), 137 (22%) had minor residual symptoms (mRS=1), and 47 (7.5%) had mild impairments (mRS=2). Eighteen (2.9%) were moderately impaired (mRS=3), 14 (2.2%) were severely handicapped (mRS=4 or 5), and 52 (8.3%) had died. Multivariate predictors of death or dependence were age >37 years (hazard ratio [HR]=2.0), male sex (HR=1.6), coma (HR=2.7), mental status disorder (HR=2.0), hemorrhage on admission CT scan (HR=1.9), thrombosis of the deep cerebral venous system (HR=2.9), central nervous system infection (HR=3.3), and cancer (HR=2.9). Fourteen patients (2.2%) had a recurrent sinus thrombosis, 27 (4.3%) had other thrombotic events, and 66 (10.6%) had seizures. The prognosis of CVT is better than reported previously. A subgroup (13%) of clinically identifiable CVT patients is at increased risk of bad outcome. These high-risk patients may benefit from more aggressive therapeutic interventions, to be studied in randomized clinical trials.