This retrospective study aimed to examine the course and prognosis of medication-related osteonecrosis of the jaw (MRONJ) initially treated conservatively and the effects of various factors affecting treatment outcomes. We evaluated 129 patients with MRONJ between January 2008 and December 2018 at a university hospital. The factors examined included sex, age, stage of MRONJ (1–3), type of bone modifying agents (bisphosphonate or denosumab), primary disease (osteoporosis or malignant tumor), medical history (diabetes and rheumatoid arthritis), use of corticosteroids, the trigger of MRONJ (teeth extraction or others), and separation of sequestrum, using logistic regression analysis. Patients with MRONJ were treated conservatively as the initial treatment in accordance with the position paper of the American Association of Oral and Maxillofacial Surgeons. Of the 129 patients, 59 (45.7%) were cured, and the condition of 70 (54.3%) remained unchanged or worsened. The overall cure rates at 12, 36, and 60 months were 25.8%, 50.8%, and 72.4% respectively. The cure rate of stage 1 was lower than that of stages 2 and 3 at 80 months. In multivariate analysis, it was found that 37 (64.9%) of 57 patients with osteoporosis as a primary disease were cured (odds ratio OR, 7.7; 95% confidence interval CI, 2.4–24.4). In addition, 40 (69.0%) of 58 patients with separation of sequestrum were cured (OR, 8.9; 95% CI, 3.4–23.5). The cure rate was significantly higher in patients with osteoporosis than in those with cancer when the treatment outcomes of primary disease were compared using the Kaplan-Meier method (p < 0.01). It was also significantly higher in patients who had separation of sequestrum than in those who did not (p < 0.05). Our results suggest that primary disease and separation of sequestrum were associated with favorable outcomes in patients with MRONJ initially treated conservatively. MRONJ had a poor prognosis with conventional treatment carried according to the stage of the disease. This was especially prominent when conservative treatment was employed for mild cases. •Of the 129 patients with MRONJ, 59 (45.7%) were cured, and the condition of 70 (54.3%) remained unchanged or worsened.•The cure rate of stage 1 was lower than that of stages 2 and 3 at 80 months.•Primary disease and separation of sequestrum were associated with outcomes in MRONJ initially treated conservatively.