Objectives: A national surveillance study to determine antimicrobial susceptibility in Haemophilus influenzae type b isolated from cerebrospinal fluid was carried out in Cuba from 1990 to 2002. Methods: Susceptibility to ampicillin, co-amoxiclav, cefotaxime, ceftriaxone, co-trimoxazole, tetracycline, chloramphenicol and rifampicin was tested by the microdilution method according to the NCCLS guidelines. Results: The 34 participating laboratories recovered 938 consecutive, non-identical isolates. All the isolates were retrieved from children aged P < 0.001). Multidrug resistance was present in 43.8% of isolates. The most prevalent phenotype was resistance to ampicillin/chloramphenicol/tetracycline/co-trimoxazole, which was detected in 29.2% of strains overall. An increase in the prevalence of resistance to these antibiotics was observed from 1990 to 2000 in the range 40.7%–54.8% for ampicillin, 40.1%–51.6% for chloramphenicol, 45.4%–58.1% for co-trimoxazole and 23%–45.2% for tetracycline. Conclusions: In Cuba, the widespread vaccination against Haemophilus influenzae type b prevented a large number of meningitis cases in children caused by strains resistant to multiple antibiotics.