Background: Multiple osteoporotic vertebral compression fractures (VCFs) have been treated with polymethylmethacrylate augmentation; however, there are cement complications and long-term fracture healing that are unknown. Transpedicle body augmenter (a porous titanium spacer) has been reported as an internal support to reconstruct the vertebral body combining short-segment fixation in burst fracture and Kümmell's disease with cord compression. Transpedicle body augmenter for vertebral augmentation (TpBA) also has been reported successfully in treating single painful VCF and vertebral metastasis lesions including pending fractures and pathologic compression fractures. To test the hypothesis that TpBA can effectively and safely treat the symptomatic multiple VCFs, this retrospective study was done by analyzing the radiographic and clinical results. Materials and Methods: We retrospectively reviewed clinical and radiographic results of TpBA for symptomatic multiple (more than two levels) VCFs in 62 patients with a total of 236 levels, i.e. 3.8 VCFs per patient. Manual reduction and TpBA via paramedian incisions with blunt dissection were done. One incision was made for two continuous levels and alternative side was selected for next incision. Mean age was 74.3 years (range, 62-87 years), and female-male ratio was 5.2:1. Anterior vertebral height and wedge angle by radiographic findings were measured at preoperative, initial follow-up and final follow-up. Clinical results were assessed by questionnaires and clinical observations. By July 2008, 58 patients returned to answer the questionnaire including quantification of pain on the visual analog scale, the response to operations (better, same, or worse after operation), returned to their pre-fracture function (yes/no) and satisfaction (a scale of 0 = completely dissatisfied to 10 = completely satisfied). Results: The mean symptom duration was 7 months, and follow-up, 48 months. The average operation time was 21 min per level, blood loss was 74 cc per level and hospitalization was 4.4 days. No patient had neurological deterioration. There was no dislodgement of implant in the final visit. Forty-eight patients (77.4%) could walk within 6-8 h after operation and the others, within 24 h. The anterior vertebral restoration was 7.3 mm initially and 6.2 mm at final follow-up. Wedge angle correction was 10.4° initially and was 9.3° at final follow-up. Pain, by the visual analog scale, was 8.5 preoperatively, 2.7 at day 7 follow-up and 2.9 at final follow-up. By the questionnaire, 52 of 58 respondents reported a decrease in discomfort after TpBA and 48 of 58 patients reported a return to normal activity after operation. The final satisfaction rate was 89.7%. Discussion: The symptoms of multiple osteoporotic compression fracture may be due to unstable fracture, radiculopathy, and global traumatic kyphosis with posture changes, which can be corrected by multiple TpBA. The transpedicle body augmenter was initially stabilized by the sinking and locking mechanism and finally by bone ingrowth. Conclusions: TpBA via a minimally invasive method led to early and medium-term clinical improvements and anatomic restoration of multiple symptomatic VCFs.