Recently, numerous articles have been published describing atypical lesions of the jaw bones related to treatment with medications based on phosphorus or analogs of its compounds, particularly bisphosphonates. Goal: To conduct a comparative analysis of the quality of life after radical surgery of the jaw in patients with medication-related osteonecrosis. A total of 82 patients were interviewed, of which 39 (47.6%) patients were in the control group (conservative treatment) and 43 (52.4%) patients in the main group had radical surgical treatment. The mean age of patients in both groups was 66.8 ± 10.03 years. Treatment of patients in the control group in terms of conventional conservative protocol included the local application of 0.05% chlorhexidine solution 1–2 times a day, antibacterial therapy (clindamycin—150 mg 4 times daily for 7 days) and NSAIDs (nimesulide). Patients in the main group (n = 43) underwent segmental resection of the jaw. Thirty days and then 6 months after the treatment, all patients were asked to assess the intensity of pain using a numerical scale, where 0 = no pain, 5 = moderate pain and 10 = the most severe pain imaginable, and to fill in the SF-36 Quality of Life Questionnaire. Results: An analysis of the results obtained with the Numeric Pain Rating Scale demonstrated that the mean pain intensity before treatment was 8.9 points in the control group, and 9.7 in the main group. These values were indicative of “unbearable pain”. After treatment (30 days), the pain score in the control group decreased and amounted to 4.1, which is evidence of the persistence of “moderate pain” in patients. In patients who underwent segmental jaw resection, the mean pain intensity was 0.5. There was no relationship with gender, but there was a direct relationship between the intensity of the pain and the stage of the process (CI = 95%). The SF-36 quality of life questionnaire showed that in the control group, who were treated conservatively, bodily pain (BoP) decreased from a score of 91.2 to 34.3, and the mental health score increased from 34.2 before treatment to 36.3 after treatment, which indicates the persistence of discomfort. The remaining parameters improved after treatment, but no complete recovery was achieved. Before radical surgery, the main group of patients also had a high level of bodily pain (95.2), but after surgery this decreased to 12.4. The remaining parameters also showed a significant difference before and after radical surgery, indicating a positive trend. Radical surgery allows us to improve the quality of life of patients, thereby confirming that surgical volume is a secondary aspect if there is no relapse after the treatment. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.