Background: Commonly, cheek tooth extraction performed in standing horses using perioperative prophylactic antibiotics, results in low post-operative complication rates. However, no studies have documented the relevance of perioperative antibiotics to the risk of post-operative complications. Objectives: To examine the association between perioperative antibiotics and post-operative complications after standing cheek tooth extraction. Study design: Retrospective cohort study. Methods: Information from clinical records and follow-up questionnaires relating to horses subjected to cheek tooth extractions between September 2016 and May 2020 was obtained. Post-operative complications and associations with perioperative antibiotics, age, sex, breed, diagnosis, tooth position, and extraction method were analysed using multivariate logistic regression. Results: A total of 305 horses were included, and of these 71 (23.3%) received perioperative antibiotics. Antibiotics were not associated with the risk of complications in 264 horses that underwent standard oral extraction; 9/49 (18.4%) that received antibiotics and 35/215 (16.3%) that did not receive antibiotics experienced postoperative complications (P = 1, RR = 0.89, OR = 1, OR CI = [0.41; 2.46]). Of 41 horses that had cheek tooth extraction through minimally invasive transbuccal cheek tooth extraction (MTE), 5/22 (22.7%) that received antibiotics and 10/19 (52.6%) that did not receive antibiotics, experienced postoperative complications. Although not statistically significant when adjusting for multiple comparisons (naïve P = 0.04, adjusted P = 0.26, RR = 2.32, OR = 4.48, OR CI = [1.05; 19.11]), this finding is clinically relevant. Younger age was also significantly associated with development of complications (P = 0.02, OR = 0.92 per year, OR CI = [0.87; 1.36]). Main limitations: The retrospective nature of the study leads to uncontrollable potential confounders and there is a relatively low number of MTE cases. Conclusion: Perioperative antibiotics were not associated with a lower complication rate in horses subjected to standard standing cheek tooth extraction. Use of perioperative antibiotics in conjunction with MTE may be merited, although further investigations are needed.