ObjectiveTo report the long‐term outcome of neurologic involvement in patients with Behçet's disease (BD).MethodsWe performed a retrospective analysis of 115 patients who fulfilled the international criteria for BD (57% male; median age 37 years [interquartile range (IQR) 30–46 years]) and had neuro‐BD (NBD) after exclusion of cerebral venous thrombosis. Factors associated with relapse of NBD, inability to perform activities of daily living, and mortality were assessed.ResultsSeventy‐eight patients (68%) presented with acute NBD and 37 (32%) presented with a progressive course. The HLA–B51 allele was carried by 49% of the patients. Overall, 46 of 115 patients (40%) had severe disability at baseline, represented by a Rankin score of ≥3. The 5‐ and 7‐year event‐free survival rates were 65% and 53%, respectively. In multivariate analysis, a positive HLA–B51 status was independently associated with the risk of NBD relapse, with an odds ratio (OR) of 3.6 (95% confidence interval [95% CI] 1.5–9.1). After a median followup of 73 months (IQR 59–102 months), 29 patients (25.2%) became dependent (were unable to perform activities of daily living) or died. Factors independently associated with poor outcome were paresis at onset (OR 6.47 [95% CI 1.73–24.23]) and location of inflammatory lesions at the brainstem on magnetic resonance imaging (OR 8.41 [1.03–68.43]). All 115 patients were treated with corticosteroids; 53 (46.1%) also took cyclophosphamide and 40 (34.8%) also took azathioprine. A trend toward longer event‐free survival was observed in patients with severe NBD (i.e., with a Rankin score of ≥3 at onset) receiving intravenous cyclophosphamide compared with those receiving azathioprine (P = 0.06).ConclusionOur findings indicate that NBD is a severe condition in which patients with the HLA–B51 allele appear to experience a worse prognosis.