A systematic review and meta-analysis. To assess and compare the effectiveness of different adjunctive treatments during tooth extraction in post-radiotherapy head and neck patients for preventing osteoradionecrosis (ORN). Two independent reviewers conducted an electronic search through PubMed, Embase, Cochrane Libraries, Scopus and Web of Science databases using relevant search terms. Additionally, references of relevant articles were manually searched for eligible studies. Included were full-length articles (randomized controlled trials (RCTs), clinical trials, or observational studies) published in English, reporting on ORN occurrence after dental extraction, with or without adjunctive interventions, in patients who had previous radiotherapy. Data extraction was similarly performed by two independent researchers. For quality assessment, bias in observational studies was evaluated using the ROBINS-I tool, while the RoB 2 tool was used for RCTs. One-arm meta-analyses estimated pooled ORN prevalence rates for different adjunctive treatments based on patient-level outcomes. For studies with direct comparisons between two modalities, pooled odds ratios for ORN were calculated using pairwise meta-analyses. This systematic review followed PRISMA guidelines and was registered in the PROSPERO database. A total of 29 studies with 1520 patients were included, comprising 4 RCTs, 4 prospective studies, and 21 retrospective observational studies. Five adjunctive treatment modalities around the time of dental extractions were identified: hyperbaric oxygen (HBO), pentoxifylline-tocopherol (PENTO), antibiotics (ABX), platelet-rich fibrin and photobiomodulation. Of the 25 observational studies included, 11 had a serious risk of bias, while all RCTs but 1 had low risk of bias. Egger's test showed no publication bias for the HBO and ABX groups (p > 0.05). Antibiotics were used in 17 studies, with significant variations in preoperative and postoperative protocols. Most studies utilized penicillin or clindamycin. The pooled prevalence of ORN was significantly lower in the HBO (4.6%), PENTO (3.4%), and ABX (3.8%) groups compared to the Control (17.6%), as indicated by the non-overlapping 95% CIs between the Control and any of the intervention groups. In studies with direct comparisons, HBO exhibited lower odds of developing ORN than the Control (odds ratio [OR] = 0.27) and ABX (OR = 0.57), although these differences were not statistically significant. HBO, PENTO, and ABX show similar reduction in ORN rates compared to no intervention. Given its cost-effectiveness and accessibility, ABX may be the most practical prophylactic modality at present.