Purpose: To assess the beneficial or harmful effects of systemic prophylactic antibiotics at extraction of teeth, apart from third molars, vs no antibiotic or placebo administration. Furthermore, if antibiotics are beneficial, to determine which type, dosage, duration and timing of administration is the most effective. Materials and Methods: The Cochrane Oral Health Group's Trials Register (to 30 January 2016) and MEDLINE (1 January 1950 to 30 January 2016) were searched. There were no language or date restrictions placed on the searches of the electronic databases. Randomised controlled trials (RCTs) of parallel group design, with a follow-up of at least 2 weeks, comparing the administration of various prophylactic antibiotic regimens vs no antibiotics to people undergoing extraction of teeth, not including third molars, were included. Outcome measures were postoperative complications/adverse events, post-operative pain and swelling. Screening of eligible studies, assessment of the risk of bias of the trials and data extraction were conducted in triplicate by three independent review authors. Results were to be expressed as risk ratios (RRs) using a random-effects model for dichotomous outcomes, with 95% confidence intervals (CIs). Heterogeneity, including both clinical and methodological factors, was to be investigated. Results: No relevant RCT was identified. Conclusions: There is no RCT to determine if the antibiotic therapy is needed at extraction of teeth, excluding third molars. Properly designed and conducted RCTs are needed to understand the role of the antibiotic therapy for tooth extraction. Keywords: antibiotic prophylaxis, local complications, tooth extraction Conflict-of-interest statement: This systematic review was self-funded and the authors have no conflict of interests to declare.