Background: Post-surgical wound infections in orthopaedic patients present clinical challenges necessitating a thorough understanding of microbial profiles and antimicrobial susceptibility patterns. This retrospective study at SMS Medical College & attached hospital investigated the bacteriological profile of 200 post-surgical wound infections over one year. Methods: Clinical data from electronic records and microbiological analysis of surgical site cultures were examined. Antimicrobial susceptibility testing was conducted and associations between patient characteristics, surgical variables and microbial profiles were assessed. Results: Staphylococcus aureus, including methicillin-resistant strains (MRSA), predominated among isolated pathogens. Other significant pathogens included coagulase-negative staphylococci, Enterococcus spp., Escherichia coli, and various Gram-negative bacteria. Antimicrobial susceptibility testing revealed concerning resistance patterns, particularly among MRSA isolates. Conclusion: This study highlights the diverse microbial etiology and antimicrobial resistance patterns in post-surgical wound infections among orthopaedic patients. Tailored infection control measures and judicious antibiotic use are crucial for optimizing patient outcomes and combating antimicrobial resistance in orthopaedic surgical settings.