Vertebral compression fractures (VCFs) are common in multiple myeloma (MM). Percutaneous vertebroplasty (PVP) is used to stabilize vertebral collapse and treat the pain. Few studies have been carried out on PVP in MM and follow-up has tended to be short. We have prospectively evaluated the safety and efficacy of PVP in the VCFs resulting from MM or plasmacytomas. Nineteen PVP were performed in 12 consecutive patients. We monitored their pain and functional status using visual analog (VAS) and Eastern Cooperative Oncology Group (ECOG) scale, respectively. For a subjective assessment, every patient was asked about his/her degree of satisfaction. The mean age of the participants was 66 yr. Significant improvement occurred 1 d after PVP according to the VAS score (7.5 pre-PVP to 3.7, P < 0.0001) and ECOG assessment (3.1 to 2.5, P = 0.002). This significant improvement was maintained after 3.2 yr of follow-up. Sixty-three percent of patients were highly satisfied with the result of the PVP and 37% were satisfied. The peri-operative mortality was 0%. Leakage of the cement outside of the vertebral body was noted in 16 of 19 injected vertebrae (84%) but none of the patients developed any clinical or neurological symptoms. At the last follow-up, no further collapse in the treated or neighboring vertebrae was noted. VCFs caused by MM or plasmacytomas can be effectively treated by vertebroplasty. PVP is associated with early clinical improvement of pain and function and can be maintained after a long follow-up without major procedure-related complications.