Eight thousand four hundred eighty-five patients with either closed (6785 patients) or open (1700 patients) extremity fractures were randomized to receive iodine povacrylex in alcohol or chlorhexidine gluconate in alcohol. The primary outcome of interest was the incidence of surgical site infections. Secondary outcomes included unplanned reoperation for fracture healing complications. Outcomes were assessed up to a specific follow-up period post-surgery. Overall, the results of the study revealed that in patients with closed fractures, iodine povacrylex significantly reduced surgical site infections compared to chlorhexidine gluconate (2.4% vs. 3.3%, P=0.049). In patients with open fractures, no significant difference was found between the two antiseptic solutions. These findings suggest that iodine povacrylex in alcohol is more effective for preventing surgical site infections in closed fracture surgeries.