Surgical site infection rates in the month following surgery vary from 1% to 5%. Due to the large number of surgical procedures conducted annually, the costs of these surgical site infections (SSIs) can be considerable in financial and social terms. Nasal decontamination using antibiotics or antiseptics is performed to reduce the risk of SSIs by preventing organisms from the nasal cavity being transferred to the skin where a surgical incision will be made. Staphylococcus aureus (S aureus) colonises the nasal cavity and skin of carriers and can cause infection in open or unhealed surgical wounds. S aureus is the leading nosocomial (hospital-acquired) pathogen in hospitals worldwide. The potential effectiveness of nasal decontamination of S aureus is thought to be dependent on both the antibiotic/antiseptic used and the dose of application; however, it is unclear whether nasal decontamination actually reduces postoperative wound infection in S aureus carriers. To assess the effects of nasal decontamination on preventing surgical site infections (SSIs) in people who are S aureus carriers undergoing surgery. In September 2016 we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched three clinical trial registries and the references of included studies and relevant systematic reviews. There were no restrictions based on language, date of publication or study setting. Randomised controlled trials (RCTs) which enrolled S aureus carriers with any type of surgery and assessed the use of nasal decontamination with antiseptic/antibiotic properties were included in the review. Two review authors independently performed study selection, data extraction, risk of bias assessment and GRADE assessment. We located two studies (291 participants) for inclusion in this review. The trials were clinically heterogeneous with differences in duration of follow-up, and nasal decontamination regimens. One study compared mupirocin (2% contained in a base of polyethylene glycol 400 and polyethylene glycol 3350) with a placebo in elective cardiac surgery patients; and one study compared Anerdian (iodine 0.45% to 0.57% (W/V), chlorhexidine acetate 0.09% to 0.11% (W/V)) with no treatment also in cardiac surgery patients. The trials reported limited outcome data on SSI, adverse events and secondary outcomes (e.g. S aureus SSI, mortality). Mupirocin compared with placeboThis study found no clear difference in SSI risk following use of mupirocin compared with placebo (1 trial, 257 participants); risk ratio (RR) 1.60, 95% confidence interval (CI) 0.79 to 3.25 based on 18/130 events in the mupirocin group and 11/127 in the control group; low-certainty evidence (downgraded twice due to imprecision). Anerdian compared with no treatmentIt is uncertain whether there is a difference in SSI risk following treatment with Anerdian compared with no treatment (1 trial, 34 participants); RR 0.89, 95% CI 0.06 to 13.08 based on 1/18 events in the Anerdian group and 1/16 in the control group; very low certainty evidence (downgraded twice due to imprecision and once due to risk of bias). There is currently limited rigorous RCT evidence available regarding the clinical effectiveness of nasal decontamination in the prevention of SSI. This limitation is specific to the focused question our review addresses, looking at nasal decontamination as a single intervention in participants undergoing surgery who are known S aureus carriers. We were only able to identify two studies that met the inclusion criteria for this review and one of these was very small and poorly reported. The potential benefits and harms of using decontamination for the prevention of SSI in this group of people remain uncertain.