Mechanical stabilization of oncological vertebral fractures with cement augmentation is the first mechanism of pain relief, with or without restoration of vertebral body height. The aim of this study was to assess the safety and efficacy of vertebroplasty for painful vertebral body fractures in patients with multiple myeloma, in each phase of the disease. The authors reviewed a consecutive group of patients with multiple myeloma who underwent vertebroplasty at our Institute between November 2003 and December 2005. Twenty-eight levels were performed on 11 patients during 14 treatment sessions. All patients suffered from intractable back pain, and presented various lesion types (with and without fractures of posterior wall, and with and without epidural disease). The preoperative median visual analog scale (VAS) score was 7. The median duration of symptoms was 1.1 months. Eight patients were ambulating with orthopaedic devices (57%) in the pre-treatment period. Improvement or complete pain relief was observed in all patients (immediately in 8 cases, and after 2 days in 6 cases). The median VAS pain score decreased to 2. There was no symptomatic procedure-related complication. There were three cases (21%) of PMMA leakage: in the disc space in one case (7%), and in the anterior spinal canal in two cases (14%). Complete removal of orthopaedic devices was obtained in five patients (36%). No new deformation or collapse of the treated vertebrae was observed during the follow-up (range 1 day-25 months). In conclusion, vertebroplasty is a safe and efficient procedure in the treatment of painful vertebral body fractures in patients with multiple myeloma, without potential contraindications, such as fractures of the posterior wall or epidural disease. We also treated three and more levels in 28% of cases in a single session without complications. Due to the early pain relief and the low complication rate, it is possible to expand the indication to vertebroplasty for the prophylactic augmentation of those vertebral bodies at risk of fracture in which significant neoplastic substitution of the body is present.