Spontaneous bacterial meningitis (BM) is more common among patients with underlying conditions, but its characteristics in previously healthy patients are not well described. We analyzed the time trends of BM in terms of characteristics, and outcomes in patients without comorbidities. Patients and methods: Single-center, prospective observational cohort study of 328 adults with BM hospitalized in a tertiary university hospital in Barcelona (Spain). We compared the features of infections diagnosed in 1982–2000 and 2001–2019. The main outcome measure was in-hospital mortality. Results: The median age of the patients increased from 37 to 45 years. Meningococcal meningitis significantly diminished (56% versus 31%,p< 0.000) whereas listerial meningitis increased (1.2% versus 8%,p= 0.004). Systemic complications were more common in the second period, although mortality did not vary significantly between periods (10.4% versus 9.2%). However, after adjusting for relevant variables, infection in the second period was associated with lower risk death. Conclusions: Adult patients without underlying comorbidities that developed BM in recent years were older and more likely to have pneumococcal or listerial infections and systemic complications. In-hospital death was less likely in the second period, after adjusting for risk factors of mortality.