Objective: It is important that during preoperative skin preparation surgical site markings are not erased. The effects of 2 common types of skin preparation solutions on surgical site markings were compared. Methods: Fasciocutaneous skin flaps were harvested and 20 random combinations of 3 letters were written on the skin flaps with a black permanent marker. Ten of the 3-letter combinations received Chloraprep (chlorhexidine gluconate, 2% w/v, plus isopropyl alcohol, 70% v/v) and the other 10 received Duraprep (iodine povacrylex [0.7% available iodine] and isopropyl alcohol [74% w/w]), both according to the manufacturer's guidelines. The skin flaps were photographed digitally before and after application of the solutions. The final pictures were assessed subjectively by 10 surgeons and then objectively to determine the change in visibility of the marking on each specimen. Results: Of the 300 letters in each group, the number of correctly identified letters was 254 (84.7%) in the Chloraprep group and 284 (94.7%) in the Duraprep group. On the basis of the visibility of skin markings, Chloraprep was 21.8 times more likely (95% credible interval, 7.3–86.7) to erase the site markings than was Duraprep. Conclusions: Skin preparation with Chloraprep erased more surgical site markings than did Duraprep.