There is currently little data on the longer term efficacy and safety of balloon kyphoplasty (BKP) in patients with metastatic vertebral compression fractures (VCFs). To prospectively assess the long-term efficacy and safety of BKP in treating thoracic and lumbar spinal metastatic fractures that result in pain or instability. Sixty-five patients (37 men, mean age: 66 years) underwent 99 BKP procedures. Patient-related outcomes of pain visual analogue scale (VAS) and Oswestry Disability Index were assessed pre- and post-operatively and after 3, 6, 12 and 24 months. Correction of vertebral height and kyphotic deformity were assessed by radiographic measurements. Mean pain VAS and Oswestry Disability Index significantly improved from pre- to post-treatment (P < 0.0001), this improvement being sustained up to 24-month follow up. A gain in height restoration and a reduction of the post-operative kyphotic angle were seen post-operatively and at 3 months although these radiographic outcomes returned to pre-operative levels at 12 months. BKP was associated with a rate of cement leakage and incidence vertebral fracture of 12 and 8%, respectively. No symptomatic cement leaks or serious adverse events were seen during the 24 months of follow up. BKP is a minimally invasive procedure that provides immediate and long-term pain relief and improvement in functional ability in selected patients with metastatic VCFs. The procedure appears to have good long-term safety.