Study Design: Case control series.Objective: The aim of this study was to evaluate and compare the effectiveness of methods to decrease surgical site infections (SSIs) following spine tumor surgery.Summary Of Background Data: With the aging population of the United States, the prevalence of cancer and associated metastatic spine disease is increasing. The most common complication of spine tumor surgery is SSI.Methods: This a single-institution case-control series of patients undergoing spine tumor surgery from June 2003 to October 2018. Patients were grouped into the following groups: Betadine irrigation and intrawound vancomycin powder (BIVP), intrawound vancomycin powder only (IVP), and patients receiving neither (NONE). The primary outcome was SSIs/wound complications.Results: One hundred fifty-one spine tumor patients undergoing 174 procedures meeting our inclusion criteria were identified. The BIVP group had 60 patients (73 procedures); the IVP group had 46 patients (47 procedures); and the NONE group had 45 patients (54 procedures). The overall infection rate was 8.6% of all procedures (15/174) and 9.9% (15/151) of all patients. Bivariate analysis comparing patients with and without infections noted the patients with SSIs had significantly higher rates of preoperative radiation treatment (53.3% in infection group vs. 25.5% in noninfection group), P = 0.02. Patients undergoing procedures in the BIVP group had a significantly lower rate of infections (2.7%) than the patients in the IVP (12.8%) and NONE (13%) groups, P = 0.04. Stepwise regression analysis was used to evaluate further factors associated with SSIs. Elevated BMI was significantly associated with SSIs in the model [P = 0.02, odds ratio (OR) 1.14]. BIVP was also protective against infections as compared to the IVP and NONE groups, P = 0.02, OR 0.02.Conclusion: BIVP led to a significant decrease in SSI rates following spine tumor surgery. Administration of BIVP is not time consuming and decreased SSI rates.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]