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Surgical site infection increases morbidity, mortality, length of hospital stay and financial cost. The effect of type ofpre-operative antiseptic agent (chlorhexidine versus povidone-iodine) onpreventing surgical site infection in clean-contaminated surgery remains unclear.Asystematic review and meta-analysis of clinical trials were conducted to determine whether chlorhexidine or povidone-iodine should be thepreferred agent forpre-operative skin antisepsis in clean-contaminated surgery, including colorectal surgery.The systematic review identified six eligible studies, containing 5281 patients. Chlorhexidine reduced post-operative surgical site infection compared to povidone-iodine (Pooled odds ratio 0.69; 95% CI 0.52-0.93; P = 0.015), but did not reduce the rate of intra-abdominal sepsis (Pooled odds ratio 0.98; 95% CI 0.53-1.86; P = 0.971).Chlorhexidine should be usedpreferentially forpre-operative antisepsis in cleancontaminated surgery, including colorectal surgery. Further large scale randomised controlled trials are required to look at the effect of chlorhexidine and povidine-iodine in operativeprocedures specific to surgical sub-speciality.