Introduction Although the role of intrasite antibiotic powder in preventing surgical site infections (SSIs) has been extensively explored in spinal surgery, it remains underevaluated in the other orthopaedic subspecialties. This systematic review examines the utilization of intrawound antibiotic powder as a prophylactic measure against SSIs in orthopaedic procedures. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, electronic searches were conducted on Ovid MEDLINE, and PubMed. Only English language, nonspine clinical studies published before May 2018 were included. Results The initial search identified 179 individual citations, and 11 studies met the eligibility criteria. All included studies were level III retrospective studies. Represented subspecialties included total joint arthroplasty, upper extremity, foot and ankle, and trauma. Eight studies demonstrated a statistically significant decrease in SSIs with the use of intrasite antibiotic powder. Discussion There are no current guidelines for the use of intrasite antibiotic powder for the prevention of SSIs in orthopaedic procedures. Despite the lack of high-quality evidence available in the literature, published smaller studies do suggest a significant protective effect. However, recommendations with regard to this technique after common orthopaedic procedures cannot yet be made.