Background The lateral transpsoas approach to the lumbar spine was developed to eliminate the need for an anterior-approach surgeon and retraction of the great vessels and has the potential for shorter operative times. However, the reported complications associated with this approach vary. Questions/purposes We identified the incidence of complications associated with the lateral transpsoas approach to the lumbar spine. Patients and Methods We retrospectively reviewed 45 patients who underwent a lateral transpsoas approach to the spine for various diagnoses between January 1, 2006, and October 31, 2010. The patients' average age was 63.3 years. Sixteen (35.6%) patients had prior lumbar spinal surgery.Twenty-one patients (46.7%) underwent supplemental posterior instrumentation. Minimum followup was 0 months (mean, 11 months; range, 0-34 months). Results Eighteen of the 45 patients (40%) had complications: 10 (22.2%) developed postoperative iliopsoas weakness, three had quadriceps weakness, and one experienced foot drop. Eight patients (17.8%) developed anterior thigh hypoesthesia, which did not fully resolve in seven of the eight patients at an average of 9 months' followup. Three patients had postoperative radiculopathies, one a durotomy, and one died postoperatively from a pulmonary embolism. Conclusions We found a 40% incidence of complications and a nontrivial frequency and severity of postoperative weakness, numbness, and radicular pain in patients who underwent a lateral transpsoas approach to the spine. Given the expanding use of the approach, a thorough understanding of the risks associated with it is essential for patient education, medical decision making, and identifying methods of reducing such complications.