Objectives: To investigate sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis. Methods: From January 2006 to July 2014, we prospectively investigated sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis in a nationwide cohort study in the Netherlands. Sex was analysed along with known predictors of unfavourable outcome using logistic regression. Results: We evaluated 1412 episodes of meningitis, 707 (50%) in men. Men more often presented with a history of remote head injury (41/667 (6%) versus 14/658 (2%) women, p 0.0002) or alcoholism (61/652 (9%) versus 21/660 (3%) women, p <0.0001). Neck stiffness was less common in men (453/651 (70%) versus 524/671 (78%) women, p 0.0004). Despite greater illness severity, women were less likely to receive treatment in an intensive care unit (odds ratio (OR) 0.72, 95% CI 0.58-0.89, p 0.003) or mechanical ventilation (OR 0.67, 95% CI 0.54-0.85, p 0.001). Women exhibited higher serum inflammatory parameters than men (median C-reactive protein 211 versus 171, p 0.0001; median erythrocyte sedimentation rate 48 versus 33, p <0.0001). Corticosteroids improved prognosis in both sexes, but absolute risk reduction was higher in women (20% versus 15%, p 0.001), although we found no significant interaction between sex and dexamethasone (p 0.38). In the multivariable analysis, male sex was an independent predictor of unfavourable outcome (OR 1.34, 95% CI 1.03-1.75, p 0.03) and death (OR 1.47, 95% CI 1.04-2.07, p 0.03). Conclusions: Our findings show sex-based differences in adults with community-acquired bacterial meningitis. Male sex is an independent risk factor for adverse outcome. It is possible that sex-based differences in immune reaction could determine a distinct response to corticosteroids. ; info:eu-repo/semantics/publishedVersion