This late-breaking discussion highlights a landmark NEJM trial comparing iodine–alcohol (DuraPrep) with chlorhexidine–alcohol (ChloraPrep) for skin antisepsis before fracture fixation. Across nearly 8,500 patients in a cluster-randomized crossover design, iodine–alcohol significantly reduced infections in closed fractures (26% relative, 0.8% absolute), with no difference in open fractures. The findings challenge long-held assumptions and suggest a practice-changing shift toward iodine–alcohol solutions, supported by strong mechanistic plausibility and broad generalizability.