Background: Streptococcus pneumoniae (S. pneumoniae) is the main cause of febrile conditions especially among children below two years and the elderly above 65 years old worldwide. In Cameroon, the frequency of S. pneumoniae as the cause of meningitis varied from 57.2% to 56.2% from 2001 to 2012. The aim of this study was to determine the susceptibility to antibiotics of S. pneumoniae involved in meningitis. Methods: A cross-sectional study was carried out during a four-year period from April 2012 to March 2016. Cerebrospinal fluid (CSF) was collected by clinicians from children less than 5 years with clinically suspected bacterial meningitis at the Mother and Child Center, Chantal Biya Foundation (MCC-CBF), in Yaounde. A probable case is a suspected clinical case with the CSF showing at least one of the following elements: turbid appearance; leukocytes ≥ 10/mm 3 , elevated protein (> 100mg/dl) or decreased glucose (<40mg/dl). Cases are confirmed when isolates are identified. The identification of S. pneumoniae was done by soluble antigens, the Binax Now® test, Gram stain, catalase test, optochin test, bile solubility and molecular serotyping.The antimicrobial susceptibility testing was carried out using the disc diffusion method on Mueller-Hinton medium with 10% sheep blood and the minimal inhibitory concentration was found using the Etest®. Results: Out of 6449 clinically suspected cases of bacterial meningitis, 384 were probable and 91 cases were confirmed. Most were isolated in children less than one year old: 54/91 (59.34%) and in boys 51/91 (56.04%). These incidences occurred mainly during the dry season. In the confirmed cases, 60 (65.93%) were due to S. pneumoniae, 9 (9.89%) due to Haemophilus influenzae B, 2 (2.19%) due to Neisseria meningitis and 20 (21.97%) due to other germs. Among the serotyped pneumococci 10/51 (19.60 %) belonged to serotype 6A/6B. Of 35 viable isolates of S. pneumoniae, 15 (42.85%) were resistant to penicillin G and 3 (8.57 %) to ceftriaxone. Conclusion: S. pneumoniae is the main etiology of childhood meningitis in Yaounde. The frequency of resistance to penicillin G was high, while moderate to ceftriaxone.