Implant removal in orthopaedics after fracture consolidation is a very common procedure but is still associated with a high rate of surgical site infection (SSI). Antibiotic prophylaxis is not recommended but advocated by some. To assess the efficacy of antibiotic prophylaxis in the prevention of early SSI following orthopaedic implant removal. A monocentric retrospective cohort study was conducted. Patients who underwent orthopaedic implant removal procedures performed from 2016 to 2021 were included. A 1:1 propensity score matching function was used to create a cohort with matched baseline characteristics and associated risk factors for SSI. Inter-cohort comparison of the occurrence of SSI (superficial or deep) and revision surgery for SSI, after propensity score matching, was performed using the odds ratio to determine the effect of preoperative antibiotic prophylaxis. In total, 965 distinct surgical procedures were included. Of these, 69 (7.15%) had an SSI, 24 (35.7%) of which required surgical revision; 214 procedures (22.18%) were performed under preoperative antibiotic prophylaxis. The propensity-matched cohort consisted of 396 procedures (198 with and without antibiotic prophylaxis). The SSI rates were 11.11% and 3.03%, respectively, in the control and antibiotic prophylaxis groups (odds ratio: 0.25; 95% confidence interval: 0.099; 0.63; P = 0.011). No difference was found for revision surgery. Preoperative administration of antibiotic prophylaxis considerably reduces the risk of SSI during the removal of an orthopaedic implant without increasing the risk of side-effects.