Third molar extraction is among the most common surgical procedures performed by oral-maxillofacial surgeons. Postoperative pain, swelling and trismus are common, especially in wisdom teeth, due to trauma to local tissues and the duration of the surgical procedure, among other factors. This systematic review was conducted in accordance with the ?Preferred Reporting Items for Systematic Reviews and Meta-Analyses? in order to answer the focused question: ?Is the local submucosal injection of tramadol effective at the control of postoperative pain in patients submitted to impacted mandibular third molar extractions??. We analyzed papers published until March 30, 2021 in the MEDLINE|PubMed, Web of Science and Cochrane Library databases. Gray literature was also consulted. Standard pairwise meta-analyses of direct comparisons were performed using a fixed-effect model; I2 ? 50 % or ? 75 % indicated moderate or high heterogeneity, respectively. Risk of bias was assessed by Cochrane Collaboration?s tool. In total, 172 participants (98 males and 74 females, aged 18 or over) from three randomized placebo-controlled trials were considered for analysis. The submucosal injection of 2 ml of tramadol adjacent to the impacted mandibular third molar was effective in controlling pain up to 6-hours after surgery, in increasing the onset of consumption of rescue analgesic and in reducing the total number of rescue analgesics used. The submucosal injection of tramadol can be considered a safe and effective procedure for pain control after impacted mandibular third molar extractions.