Background <p>Intrawound vancomycin powder (IVP) has emerged as a promising adjunctive strategy for reducing surgical-site infections (SSIs) in orthopedic procedures. Its application spans various surgical contexts, including spine surgery, joint arthroplasty, trauma, sports surgery, and tumor-related interventions. </p> Objective <p>This narrative review aims to synthesize current evidence on the efficacy, safety, and optimal application of IVP across orthopedic subspecialties.</p> Methods <p>A comprehensive literature review was conducted to evaluate the outcomes of IVP use in orthopedic surgery. Relevant studies were identified and analyzed for infection rates, safety, dosing, and complications.</p> Results <p>Numerous studies report reduced SSI rates with IVP, particularly in high-risk procedures. However, findings remain mixed, with some studies citing inconsistent efficacy and concerns about bacterial resistance, wound complications, and delayed healing. IVP achieves high local antibiotic concentrations with minimal systemic absorption and is generally well tolerated. Common doses range from 1 to 2 g, though optimal dosing remains unstandardized. Adverse effects are rare but include hypersensitivity and altered microbial flora.</p> Conclusion <p>While IVP shows potential as an effective adjunct to prevent SSIs in orthopedic surgery, especially in high-risk cases, definitive conclusions are limited by heterogeneous data. Further high-quality randomized controlled trials are necessary to establish standardized protocols, assess long-term safety, and guide clinical practice.</p>