Aims: To assess prospectively the effectiveness and safety of Cortossª, a new synthetic, biocompatible, highly radiopaque composite in the percutaneous augmentation of vertebral compression fractures. Methods: Patients with severe pain (> 50mm VAS) associated to radiographic evidence of osteoporotic or malignant vertebral compression fracture(s). Cortoss was injected with the help of a syringe-catheter system introduced into a 10 to 11-gauge needle under continuous ßuoroscopic control. All leakages and adverse events were to be reported. Assessments were made before vertebroplasty (bv) and after 3 days (3d), 1 week (1w), 1 month (1m), 3 (3m) and 6 months (6m). Results: Fifty-eight interventions were performed in 53 patients. Mean pain scores (mm VAS) decreased from 69 (bv) to 39 (3d), 39 (1w), 31 (1m), 23 (3m), 26 (6m). A mean (range) of 4.3 (1.5–8) mL of Cortoss was injected per vertebral body. Augmented vertebral bodies remained stable over time. Leakage of Cortoss occurred in 76% of interventions. No pulmonary emboli or persistent nerve root or medullary irritation occurred in association to leakage of Cortoss. One patient required local corticosteroid injection for pain associated to soft tissue leakage. The visibility of Cortoss on all imaging techniques was excellent and its use generally considered to be easy. Conclusions: The use of Cortoss for augmentation of vertebral compression fractures appears to be safe and effective and represents a promising biocompatible alternative to PMMA thanks to its radiopacity and ease of use.