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A study to investigate the pattern of resistance and production of extended spectrum beta-lactamases (ESBLs) in Staphylococcus aureus isolates in three tertiary health institutions in Nigeria was reported. S. aureus is one of the most implicated human pathogens and has over the years been reported to be associated with several infections. The increasing resistance pattern of S. aureus to commonly used antibiotics and Extended Spectrum Beta-lactamases producing clinical strains of S. aureus were assessed by the Kirby-Bauer technique and the modified disc diffusion technique respectively. Seventy (70) positive cultures of S. aureus from Hospitalized patients in three Tertiary Health Institutions in Nigeria namely: National Orthopaedic Hospital, Lagos; University of Ilorin Teaching Hospital, Ilorin and, University College Hospital, Ibadan, were obtained from wounds and High Vaginal Swabs. The decline susceptibility patterns in S. aureus revealed in this study has always not been given a very serious attention. This contributes to a high prevalence of resistance among the clinical isolates and, thus, may be responsible for increased virulence and successful in-vivo survival especially in developing countries where there is extensive application and misuse of antibiotics. Extended Spectrum Beta-Lactamases (ESBLs) are plasmid-mediated enzymes responsible for the development of antibiotics resistance. Thirteen (18.57%) ESBLs producer observed in this study correlates with recently reported cases of high incidence of S. aureus super bug.