The present retrospective study was designed to compare the pain relief, surgery duration, life quality, survival time and relative prognostic factors in multiple myeloma (MM) bone disease patients with different surgical sites. A total of 65 cases were enrolled and divided into two groups. Group A included patients with lesions located in the spine, while Group B included patients with lesions located in the long bone or soft tissue. Pain relief was measured by the visual analogue scale (VAS), neurological impairment was determined according to Frankel classification, and survival was assessed by the Kaplan-Meier method. Cox regression analysis was also used to estimate the effect of factors on the prediction of survival. The hospitalization time, preoperative duration of symptoms, method of surgery, complications, recurrence and survival time were evaluated and compared retrospectively. Pain relief and improvement of life quality were observed in all the patients in groups A and B. No significant differences were detected for the majority of parameters compared between groups A and B, with the exception of the surgery duration, as well as the postoperative VAS score at 1 and 6 months after surgery. The multivariate Cox regression analysis revealed several risk factors significantly associated with survival, including the preoperative VAS score, postoperative chemotherapy, prothrombin time activity (PTA), albumin, lactate dehydrogenase and urine protein level. In conclusion, surgical treatment was an effective therapeutic method in patients with MM. Postoperative analgesic use should be individualized according to the different surgical sites and postoperative periods. Furthermore, preoperative pain, PTA, albumin, urine protein level and postoperative chemotherapy are associated with prognosis.