ObjectiveWe sought to determine the prevalence and antimicrobial susceptibility pattern of methicillin-resistantStaphylococcus aureus(MRSA) isolated from the clinical samples at a tertiary care hospital in Nepal.MethodsCross-sectional, observational study design.Study settingThe study was carried out at a tertiary care facility, the largest public hospital, Tribhuvan University Teaching Hospital (TUTH), Nepal.ParticipantsA total of 7433 clinical samples from hospital inpatients and outpatients available in the TUTH microbiology laboratory were examined. The study included clinical samples from the patients of either sex and across all age groups that had been clinically determined to haveS. aureusinfections.ResultsOf 7433 clinical samples analysed,S. aureuswas recovered from 499 (6.71%). The prevalence of MRSA was discovered to be 26.4% (95% CI 21.6% to 30.4%). The major sources of MRSA were pus, 71 (18.5%). MRSA isolates encountered 100% resistance to penicillin and cloxacillin, followed by ciprofloxacin (80.5%), erythromycin (79.8%), cephalexin (64.9%), cotrimoxazole (61.1%) and clindamycin (58.5%). Chloramphenicol (17.9%), and gentamicin (27.4%), on the other hand, exhibited minimal resistance. None of the isolates were resistant to vancomycin (0.0%). Prevalence of multidrug resistance (MDR) was markedly higher in MRSA, 94.05% (95% CI 89.4% to 98.6%), compared with methicillin-sensitiveS. aureus, 52.12% (95% CI 46.2% to 57.8%).ConclusionOur study indicated a high rate of MRSA and MDR-SA (Multidrug-resistant Staphylococcus aureus) prevalence in a Nepalese tertiary care hospital. Therefore, given the widespread burden of MRSA and the threat of the emergence of resistance to commonly used antibiotics, there is a need for the development, adoption and enforcement of appropriate control policies in these hospital settings. Regular surveillance, reporting mechanism as well as prudent use of antimicrobial agents are crucial to combating the progression of MDR-MRSA prevalence and antibiotic resistance.