Abstract Background Studies have implicated Staphylococcus aureus as the leading cause of septicemia in the Tamale metropolis of Ghana. The aim of this study was to determine the prevalence and antibiotic susceptibility of S. aureus and Methicillin Resistant S. aureus (MRSA) in the environments of three hospitals in Ghana. Methods A total of 120 swab samples were taken from door handles, stair railings and other points of contact at Tamale Teaching Hospital, Tamale Central Hospital and Tamale West Hospital. The swab samples were directly plated on Mannitol Salt and Baird Parker agar plates and incubated at 37 °C (± 2) for 18–24 h. An antibiotic susceptibility test was performed using the Clinical Laboratory Standard Institute’s guidelines. Isolates resistant to both cefoxitin and oxacillin were considered to be MRSA. Results A total of 47 (39%) positive S. aureus samples were isolated from all three hospitals, of which, eight (17%) were putative MRSA isolates. One MRSA isolate was resistant to all the antibiotics used (cefoxitin, oxacillin, ciprofloxacin, erythromycin, tetracycline, ampicillin, streptomycin and sulfamethoxazole-trimethoprim). Five of the MRSA isolates were multi-drug resistant, whilst the other three were resistant to only two antibiotics. All the multi-drug resistant MRSA isolates were resistant to at least four antibiotics. The percentage of isolates resistant to oxacillin, ampicillin, ciprofloxacin, tetracycline, streptomycin, erythromycin, and sulfamethoxazole/trimethoprim were 17, 13, 9, 28, 89, 13 and 11% respectively. Conclusion The high multi-drug resistance of MRSA in hospital environments in Ghana reinforces the need for the effective and routine cleaning of door handles in hospitals. Further investigation is required to understand whether S. aureus from door handles could be the possible causes of nosocomial diseases in the hospitals.