OBJECTIVE To evaluate invasiveness index as a potential predictor of spine surgical site infection (SSI) after spinal fusion, revision fusion, or laminectomy. DESIGN Retrospective cohort study. SETTING Single, large, academic medical center. PATIENTS Adults undergoing spinal fusion, revision fusion, or laminectomy. METHODS Data were obtained from electronic hospital databases; cases of SSI were extracted from the infection control database using National Healthcare Safety Network (NHSN) definitions. For each case, an invasiveness index, determined by surgical approach, procedure, and number of spine levels treated, was calculated using current procedural terminology (CPT) billing codes. Statistical analyses were performed using univariate and multivariate logistic regression models. RESULTS In total, 3,143 patients met inclusion criteria, and 43 of these developed SSI. Multivariate regression showed that advanced age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.005-1.05, for each year of life) and invasiveness index (medium invasiveness index OR, 5.36; 95% CI, 1.92-14.96; high invasiveness index OR, 14.1; 95% CI, 4.38-45.43) were significant predictors of infection. In subgroup analyses of spinal fusion patients, morbid obesity (OR, 2.542; 95% CI, 1.08-5.99), trauma (OR, 2.41; 95% CI, 1.05-5.55), and invasiveness index (medium invasiveness index OR, 5.39; 95% CI, 1.56-18.61; high invasiveness index OR, 13.44; 95% CI, 3.28-55.01) were significant predictors of SSI. Models containing invasiveness index were compared to NHSN models and demonstrated similar performance. CONCLUSIONS Invasiveness index is a predictor of SSI after spinal fusion and performs similarly to NHSN models. Invasiveness index shows promise as a potential risk stratification tool that is easily calculated and is available preoperatively. Infect Control Hosp Epidemiol 2016:1-7.