We conducted a prospective, observational study in Barcelona (Spain) to determine changes in the spectrum of adult patients with bacterial meningitis (BM) over a 29-year period.The observation was divided into two periods: 1982–1995 (I) and 1996–2010 (II). All patients underwent clinical examination on admission and at discharge following a predefined protocol.We evaluated 635 episodes of BM. The most frequent etiologic agents were Neisseria meningitidis and Streptococcus pneumoniae in periods I and II, respectively. Patients in period II were older (Median: 47.5 [95%CI: 23.0–64.5] vs. 58.0 [39.0–73.0] years, P < 0.0001), had a longer interval from admission to therapy (Median: 2.3 [95%CI: 1.0–5.0] vs. 4.0 [2.0–12.0] hours, P < 0.0001), and more frequently had co-morbid conditions (39.1% vs. 62%, P < 0.0001). Meningococcal meningitis decreased by 66% (P < 0.0001), whereas meningitis by Listeria monocytogenes increased by 110% (P = 0.0007) in period II. There were no differences in the overall case-fatality and post-meningitic sequelae rates between both periods.BM in adult patients has substantially changed over 29 years in terms of population affected, aetiology, and management, but not in terms of its overall mortality rate and appearance of post-meningitic sequelae.