429 patients scheduled for major orthopaedic surgery were randomized to nasal decolonization with either an off-the-shelf povidone-iodine solution, a specialized Skin and Nasal Antiseptic povidone-iodine solution (3M), or placebo saline swabs. Patients were assessed for Staphylococcus aureus (S. aureus) colonization of the nares. Nasal S. aureus colonization rate was assessed at 4 hours and 24 hours after decolonization. Similar numbers of patients in each group had positive baseline S. aureus colonization. At 4 hours, nasal colonization rate significantly differed between the three groups, and was lowest in the specialized SNA PI solution group. By 24 hours, nasal colonization rate did not significantly differ between the three groups.