A retrospective study was conducted in 179 consecutive patients (48 males, 131 females; mean age: 72.0 ± 8.59 years; range: 51–93) with single symptomatic acute amyelic osteoporotic vertebral fracture presenting between September 2004 and September 2005 to the Santa Lucia Foundation in Rome, Italy. Vertebral fractures usually become manifest due to pain which can be debilitating. Treatment depends on the presence or absence of spinal cord involvement. In the first case, surgical stabilization is mandatory. In the second case, treatment may be performed either by conservative medical therapy (CMT) or percutaneous vertebroplasty (PVT). The aim of this study was to evaluate the effectiveness, costs and cost-effectiveness of percutaneous vertebroplasty. After 2 weeks of analgesic therapy, 153 patients presented refractory pain and were offered treatment by PVT. A total of 58 patients accepted and underwent PVT (PVT group), while 95 refused and underwent conservative medical therapy (CMT group). Follow-up was performed by specialist consults, spine radiography and MRI and a self-assessment questionnaire evaluating pain using a Visual Analogue Scale (VAS) and function using an ambulation and an Activities of Daily Living (ADL) scale. A 12-month follow-up was obtained in 86 of 95 (90.5%) CMT group patients and 54 of 58 (93.1%) PVT group patients. Significant reduction of VAS and improvement of ambulation and ADL was observed in both groups at 1 week and 3 and 12 months (P < 0.05; Wilcoxon signed rank test), however, these results were significantly superior in the PVT group at 1 week and 3 months (P < 0.05; Mann–Whitney U test). Average cost per patient at 1 week and 3 and 12 months were respectively 755.49 ± 661.96, 3791.95 ± 3341.97 and 4299.55 ± 3211.53 € (CMT group) and 3311.35 ± 0.32, 3745.30 ± 3.59 and 4101.05 ± 755.41 € (PVT group). PVT resulted significantly more cost-effective than CMT with regards to the three scales at 1 week (P < 0.05; Mann–Whitney U test). At 3 months PVT was more cost-effective than CMT with regards to the three scales, however, the difference was significant only with regards to ambulation. No significant differences in cost-effectiveness where found between the two groups at 12 months. PVT should be considered the treatment of first choice in symptomatic acute amyelic osteoporotic vertebral fractures with refractory pain after a short period of analgesic therapy.