To study the prevalence and antibiotic resistance patterns ofMDR S. aureus frompyogenic infections in diabetic and non-diabetic patients fromdifferent hospitals in Rayalaseema, Andhra Pradesh, South India. Total 70 Staphylococci were isolated from 90 individuals including both diabetic and non-diabetic patients and 44 were confirmed as S. aureus. Subsequently antibiotic resistant patterns were carried out using 11 standard antibiotics according to CLSI. Out of 44 S. aureus, 40 were isolated fromnon-diabetic patients and 4 from diabetic patients. The highest resistance toAmpicillin (100%) followed byPenicillin (90.90%),Methicillin (81.81%),Vancomycin (77.27%),Co-trimoxazole (52.27%),Tetracycline (38.63%), andCephalexin, Ciprofloxacin and Oflaxacin (20.45%). The lowest resistance to chloramphenicol and Cloaxacillin were minimum with an incidence of 15.9% and 11.36% respectively. The observations of the present study call for a detailed investigation on the epidemiology of S. aureus in this region and to find out the measures for eliminating the incidence of S. aureus from this region.