96 patients with closed fractures undergoing open reduction and internal fixation were randomized to receive either topical vancomycin powder plus systemic antibiotic prophylaxis (n=48) or systemic antibiotic prophylaxis alone (n=48). The primary outcome of interest was the incidence of fracture-related infection (FRI). Secondary outcomes included clinical signs of infection, radiological evidence of bone lysis around the implant, impaired fracture healing, and the presence of specific pathogens. Outcomes were assessed up to 6 weeks post-surgery. Overall, the results of the study revealed no statistically significant difference in the incidence of FRI between the two groups (p=0.494). While the intervention group showed fewer cases of bone lysis, it did not translate into a significant reduction in infection rates. The study concludes that topical vancomycin does not significantly reduce FRIs in closed fractures treated with open reduction and internal fixation.