OBJECTIVE To identify risk factors for surgical site infections (SSIs) after spine operations. DESIGN Case-control study of SSIs among patients undergoing spine operations. SETTING An academic health center. PATIENTS We studied patients undergoing spinal fusions or laminectomies at the University of Iowa Hospitals and Clinics from January 1, 2007, through June 30, 2009. We included patients who acquired SSIs meeting the National Healthcare Safety Network definition. We randomly selected controls among patients who had spine operations during the study period and did not meet the SSI definition. RESULTS In total, 54 patients acquired SSIs after 2,309 spine operations (2.3 per 100 procedures). SSIs were identified a median of 20 days after spinal fusions and 17 days after laminectomies; 90.7% were identified after discharge and 72.2% were deep incisional or organ-space infections. Staphylococcus aureus caused 53.7% of SSIs. Of patients with SSIs, 64.9% (fusion) and 70.6% (laminectomy) were readmitted and 59.5% (fusion) and 64.7% (laminectomy) underwent reoperation. By multivariable analysis, increased body mass index, Surgical Department A, fusion of 4-8 vertebrae, and operation at a thoracic or lumbar/sacral level were significant risk factors for SSIs after spinal fusions. Lack of private insurance and hypertension were significant risk factors for SSIs after laminectomies. Surgeons from Department A were more likely to use nafcillin or vancomycin for perioperative prophylaxis and to do more multilevel fusions than surgeons from Department B. CONCLUSIONS SSIs after spine operations significantly increase utilization of healthcare resources. Possible remediable risk factors include obesity, hypertension, and perioperative antimicrobial prophylaxis. Infect Control Hosp Epidemiol 2016;1458-1467.