Background <p>The management of medication-related osteonecrosis of the jaw (MRONJ) is challenging, and there is ongoing debate over whether medical or surgical treatment is the gold standard. The aim of this retrospective study is to investigate the efficacies of medical and surgical treatments of MRONJ and comparatively evaluate their outcomes.</p> Methods <p>This study analyzed 116 MRONJ lesions in 102 patients, divided into medical and surgical treatment groups. Outcomes after 12 months were categorized into four healing response groups. Associations between variables and outcomes were assessed using Chi-Square and Fisher’s exact tests.</p> Results <p>All stage 1 MRONJ lesions showed complete healing (H1), regardless of the treatment modality. In stage 2 MRONJ lesions, no statistically significant difference was found between two treatment approaches (<i>p</i> = 0.693). In contrast, for stage 3 MRONJ lesions, treatment outcomes differed significantly between groups (<i>p</i> = 0.007). Secondary osteonecrosis occurred in 71.4% of stage 3 lesions that were treated surgically (<i>p</i> = 0.003). Spontaneous sequestration occurred in 56 lesions as an outcome of the medical therapy(n:71). A statistically significant correlation was found between healing outcomes and spontaneous sequestration (<i>p</i> &lt; 0.001).</p> Conclusions <p>In conclusion, the antibiotherapy protocol is a safe and effective non-surgical option for MRONJ management, promoting necrotic bone sequestration with reduced complications and high recovery potential.</p> Trial registration <p>This study is retrospectively registered. Clinical Trial Registration (ID NCT06917846, Date 20250409, [ <a href="https://clinicaltrials.gov/study/NCT06917846">http://clinicaltrials.gov/study/NCT06917846</a>]).</p>