Over the last four decades, methicillin-resistant Staphylococcus aureus (MRSA) has spread throughout the world and become highly endemic in many geographical areas. This pathogen causes severe morbidity and mortality in hospitals worldwide. MRSA is also considered a major community acquired pathogen throughout the world. MRSA is implicated in serious clinical conditions such as bacteremia, pneumonia, and intra-abdominal infection. The objective of this study was to determine the prevalence of MRSA in Accra, Ghana, and also to determine its antibiotic susceptibility profile. Two hundred and fifty Staphylococcus aureus isolates from routine microbiological specimens were collected from five hospitals in Accra. MRSA screening assay was used to screen for MRSA. Disc diffusion method (Kirby-Bauer) was used to determine the susceptibility of the MRSA. The MRSA screening assay, which is very close to the polymerase chain reaction in terms of specificity and sensitivity, showed that 84 of the 250 isolates were MRSA, giving a prevalence rate of 33.6%. MRSA strains were susceptible to erythromycin; 63 out of the 84 MRSA isolates were susceptible representing 75%. This was followed by gentamicin 46 (54.7%), cotrimoxazole 35 (49%), cefuroxime 33 (38%), flucloxacillin 24 (28.6%), and ampicillin 13 (15.5%). Penicillin 4 (4.8%) and tetracycline 6 (7.1%) were the least susceptible. The findings from this study emphasize the need for continual surveillance of MRSA and of antibiotic resistance in general.