Surgical site infections (SSI) are undesired and troublesome complications after spinal surgery. The reported infection rates range from 0.7 to 11.9%, depending on the diagnosis and the complexity of the procedure. Besides operative factors, patient characteristics could also account for increased infection rates. Because the medical, economic and social costs of SSI are enormous, any significant reduction in risks will pay dividends. The purpose of this study is to compare patients who developed deep SSI following lumbar or thoracolumbar spinal fusion with a randomly selected group of patients who did not develop this complication in order to identify changeable risk factors. With a case-control analysis nested in a historical cohort of patients who had had a spinal fusion between January 1999 and December 2008, we identified 36 cases with deep SSI (CDC criteria). Information regarding patient-level and surgical-level risk factors was derived from standardized but routinely recorded data and compared with those acquired in a random selection of 135 uninfected patients. Univariate analyses and a multivariate logistic regression were performed. The overall rate of infection in 1,615 procedures (1,568 patients) was 2.2%. A positive history of spinal surgery was associated with an almost four times higher infection rate (OR = 3.7, 95% BI = 1.6-8.6). The risk of SSI increased with the number of levels fused, patients with diabetes had an almost six times higher risk and smokers had more than a two times higher risk for deep SSI. The most common organism cultured was Staphylococcus aureus. All infected patients underwent at least one reoperation, including an open débridement and received appropriate antibiotics to treat the organism. Patients who had had a previous spinal surgery are a high-risk group for infection compared with those that never had surgery. Total costs associated with preventive measures are substantial and should be compensated by health care insurance companies by means of separate clinical pathways. High-risk patients should be informed about the increased risk of complications.