BACKGROUND: Traditional methods of pre-operative hair removal include among others chemical depilation and razor shaving. The effect of this practice on SSI is yet to be fully elucidated in our environment. OBJECTIVE: The aim of the study was to compare the effects of chemical depilation and razor shaving on post-operative wound infection at the NAUTH, Nnewi. PATIENTS AND METHODS: During the study period of August 2015 to January 2017, 120 patients undergoing only clean surgeries in hair-bearing areas in NAUTH Nnewi were assessed for eligibility and randomised into two methods of pre-operative hair removal using a razor, and cream (Reckitt Benckiser Dublin UK). The independently assessed outcome measures were the completeness of hair removal using the Likert scale and postoperative wound infection using the Modified Southampton Wound Grading System post-operatively on 3rd, 5th,7th and 30th day. Data were analysed using SPSS version 21 Chicago Illinois, statistical significance was inferred at P value ≤ 0.05. RESULTS: A total of 100 patients were studied with twenty excluded on account of co-morbidities (9) and non-completion of the study (11).The overall prevalence of surgical site infection (SSI) was 18.0% (18/100) involving 7(14.0%) patients in the depilatory cream group and 11(22.0%) in the razor shaving group. The difference in the rate of SSI was not statistically significant (p=0.436). Of the 50 patients who had hair removal by depilatory cream, hair was completely removed in 47 (94.0%) compared to 38 (76.0%) patients in the razor shaving group (p=0.012). Skin injuries were noted in 21 (42.0%) patients in the razor group and 1 (2.0%) patients who had chemical depilation (p = 0.0001). In addition, there was no case of allergic reaction in all the subjects who had chemical depilation. CONCLUSION: There was no significant difference in SSI rates between the chemical depilatory group and razor shaving group. However, pre-operative hair removal by chemical depilation caused fewer skin injuries and was more effective in removing hair when compared with razor shaving. Keywords: Surgical site infection, depilatory cream, razor shaving