Hospital-acquired infections, including surgical site infections (SSIs), pose a concerning challenge because of the growing resistance to multiple drugs, largely influenced by extensive prophylactic antimicrobial therapy. Although SSIs are well documented in advanced hospitals in developed nations, their prevalence and bacterial profiles are inadequately reported in low- and middle-income nations such as Nepal. This retrospective cohort study explored the prevalence of orthopaedic SSIs in relation to bacterial etiology and antimicrobial resistance. We examined the surgical and bacteriological records of patients suffering SSIs (clean or clean-contaminated wounds) within a month of their surgical procedures between January 2020 and June 2022 at the National Trauma Center, Kathmandu, Nepal. The prevalence of orthopaedic SSIs among hospital-visiting patients was 31.2% (448/1,438; 95% CI: 28.8-33.5). There were 341 (76.1%) males and 361 (80.6%) adults with SSIs. Knee/joint infections (n = 141, 31.5%) were predominant. An SSI typically occurs 7 days after surgery. Enterobacterales were dominated by Escherichia coli (n = 54, 40.9%), whereas nonfermenters gram-positive cocci (GPC) were dominated by Pseudomonas aeruginosa (n = 69, 81.2%) and Staphylococcus aureus (n = 216, 93.5%), respectively. Enterobacterales, nonfermenters, and GPC exhibited penicillin resistance at 74.5%, 29.8%, and 65.1%, respectively, whereas cephalosporin resistance was exhibited at 48.3%, 57.1%, and 49.6%; fluoroquinolone resistance at 25.9%, 40.5%, and 25.7%; and aminoglycoside resistance at 21.5%, 43.2%, and 17.3%. One-third of orthopaedic surgeries resulted in SSIs, mainly caused by S. aureus. Fluoroquinolones and aminoglycosides were moderately effective in treating bacterial SSIs, whereas penicillins and cephalosporins were the least effective. Nonfermenters exhibited higher antimicrobial resistance compared with Enterobacterales and GPC.