Objective To evaluate the efficacy and safety of balloon kyphoplasty in the treatment of painful multi-vertebral osteoporotic compression fractures. Methods From October 2002 to April 2007, 42 patients (96 vertebrae) with painful multi-vertebral osteoporotic compression fractures underwent kyphoplasty. The group included 14 men and 28 women with an average age of 72.5 years (range 56-91 years). Each pro-cedure included insertion and insertion of balloon, fracture reduction and cement filling under "C"-arm monitoring. Preoperative and postoperative pain level, SF-36 score, vertebral height restoration, local kypho-sis correction and complications were recorded and analysed. Results All 42 patients tolerated the opera-tion well and were followed up for average 31.4 months (range 12-71 months). The mean VAS pain score decreased significantly from 7.1±2.4 preoperatively to 2.7±1.3 postoperatively, the mean height of anterior and medial vertebral body were (1.8±0.5) cm, (1.6±0.6) cm preoperatively and (2.3±0.6) cm, (2.2±0.7) cm postoperatively. No significant change of posterior vertebral height was recorded postoperatively.The mean correction of local kyphosis was 9.2°at each level. 6 of 8 subscahs measured by SF-36, including physical function, role function, bodily pain, vitality, role emotion, mental health, were significantly improved by the operation. Complications were found in 7 patients including 6 cases of cement leakage with no clinical symptoms (intradiscal cement leakage in two cases, paravertebral vessel leakage in two cases, paravertebral leakage in one case and cement leakage into canal in one case), and 1 case of pulmonary embelization with symptoms relieved after conservative treatment. Conclusion Kyphoplasty is effective and relatively safe for multi-vertebral osteoporotic compression fractures.