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Retrospective review of prospective collected data on 22 patients.To describe our initial clinical experience and outcomes with the extreme lateral interbody fusion (XLIF) approach for spinal diseases requiring access to the thoracic cavity.Minimally invasive anterior approaches to the thoracic spine have traditionally consisted of thoracoscopic and mini-open thoracotomy techniques. We present our initial experience with employing the XLIF technique to treat thoracic spine diseases.Clinical, radiographic, operative, postoperative, and functional outcomes were analyzed.A total of 22 patients (15 females, 7 males, average age 64.6 y) with isolated thoracic and thoracolumbar spine diseases were treated between 2005 and 2009. The indications for surgery included degenerative scoliosis (11), pathological fractures from tumors (2), adjacent level disease from prior fusions (5), thoracic disc herniations (3), and discitis/osteomyelitis (1). A total of 47 levels were treated. In the subset of patients treated for degenerative scoliosis, the mean preoperative and postoperative coronal Cobb angles were 22 and 14, respectively. The mean preoperative and postoperative sagittal angles were 39 and 44, respectively. The average estimated blood loss and length of stay were 227.5 mL and 4.8 d, respectively. Three complications consisting of wound infection, subsidence, and adjacent level disease requiring additional procedures were encountered. There were no neural, vascular, visceral injuries, or death. At a mean follow-up of 16.4 months (range, 3-50), we observed a 95.5% substantial clinical benefit. All patients who had reached a minimum of 6 months (95.5%) demonstrated radiographic evidence of fusion.The XLIF technique can be expanded to treat diseases in the thoracic spine. Although the magnitude of deformity correction achieved is less than that of the traditional open approaches, the lesser invasiveness of this technique may be tolerable for the elderly and in patients with significant medical comorbidities.