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The aim of this review was to report on the use of local application of vancomycin in various realms of orthopaedic surgery, discuss limitations on current studies, and identify potential areas for future research. Vancomycin powder has been used effectively and extensively to prevent surgical site infection in spine surgery, leading to an increased use in other orthopaedic subspecialties. Vancomycin soaking is an emerging technique used in anterior cruciate ligament reconstruction to presoak grafts before implantation. The potential effect to surrounding structures that result from using high localized concentrations of vancomycin is an area of the literature that may be beneficial to further understand. Given the increasing use of locally applied vancomycin, it is essential to understand the spectrum of benefits and safety and continue to analyze the results of emerging studies to guide the future safe practice of surgeons. It is also important to consider population-level effects, such as antimicrobial resistance, that may be associated with more frequent use of vancomycin. Our review concluded that the current literature is limited to mainly retrospective or observational studies, and it would be beneficial to conduct more randomized control trials and prospective studies.