BACKGROUND: Surgical site infection is a major factor affecting the outcome in pediatric surgical care. The burden of surgical site infection is higher in sub Saharan Africa (SSA) than in the developed nations. In Nigeria studies have shown that surgical site infection is higher in the pediatric age group and is associated with increase in cost of surgical care as well as increase in morbidity and mortality. In recognition of these problems the Center for Disease Control (CDC), USA, suggested preoperative skin preparation with an antiseptic agent such as chlorhexidine gluconate, iodine/iodophors and alcohol to reduce the resident bacteria around the operative site as a measure to reduce post-operative surgical site infection. Some studies have compared the effectiveness of the various antiseptic agents in adult populations. Studies considering the additive effect of using a combination of antiseptic agents on the rate of surgical site infection are scanty. The aim of this study was to compare the rate of surgical site infection in children undergoing clean elective surgery following preoperative skin preparation with povidone iodine alone and povidone iodine with alcoholic chlorhexidine. MATERIALS AND METHODS: This was a prospective randomized controlled cohort study in which the study population were divided into two groups of equal sizes (60 patients each) i.e. the treatment group (Group A) which had skin preparation with alcoholic chlorhexidine (2% chlorhexidine gluconate in 70%isopropyl alcohol [Chloraprep] ) and 10% povidone iodine; and the control group (Group B) whose skin was prepared with 10% povidone iodine only. Skin swabs were taken from both groups before and after the skin preparation and subjected to culture, and then the bacteria colony was counted. The patients were then followed up for 30 postoperative days for evidence of surgical site infection (SSI). RESULTS: Of the one hundred and twenty patients in this study, one hundred and two were males and eighteen female (M: F=5.2:1). The mean age was 5.12years with a standard deviation of 0.32. Skin antisepsis with the respective antiseptic agents brought about 99.9% and 95.0% reduction in the bacteria colony count for group A and B respectively (P =0.011 and 0.002 for group A & B respectively). Out of the 120 patients, four patients had SSI, giving an overall infection rate of 3.3%.Three of these were from the control group (Group B) that had skin preparation with10% povidone iodine only (SSI rate of 5%), while the one other is from the treatment group (Group A) which had skin preparation with alcoholic chlorhexidine and povidone iodine (SSI rate of 1.67%) (p = 0.619). Three of the SSI (the one from Group A and two from Group B) was superficial incisional while one (from Group B) was deep incisional. The organism involved in the SSI was staphylococcus spp in three cases (the one from Group A and two from Group B) and Escherichia coli in the remaining one. The SSI was complicated by partial wound dehiscence in three patients(the one from Group A and two from Group B) and complete wound dehiscence in the remaining one from group B. SSI was also associated with readmission of two patients in group B and increase in the average cost of care (statistically significant. P=0.00<0.001). CONCLUSION: This study has shown that the sequential use of 2% alcoholic chlorhexidine and 10% povidone iodine for skin preparation before surgery for clean elective cases significantly reduces the native bacteria flora and reduces the rate of surgical site infections. We recommend this as an acceptable unit protocol for preoperative skin preparation in children.