Background ContextWhile some studies have demonstrated that ambulatory surgery centers (ASCs) are associated with reduced costs of orthopedic procedures, there is no consensus in the current literature as to the impact of ASCs versus hospital-based outpatient departments (HOPDs) on anterior cervical discectomies and fusions (ACDFs). PurposeThis study sought to 1) compare immediate procedure reimbursements, patient out-of-pocket expenditures, and surgeon reimbursements for ACDFs performed at ASCs versus HOPDs and 2) identify factors predicting facility utilization. Study DesignRetrospective cross-sectional study. Patient SampleWe identified ACDF procedures performed at an ASC or HOPD in commercially-insured patients aged 18-64. Outcome MeasuresPayment variables were calculated from claims within 3 days preoperatively and postoperatively. MethodsMultivariable regression models assessed a) associations between the surgery setting and payment variables and b) factors associated with the surgery setting. ResultsWe included 18,191 ACDFs (14.8% ASC, 85.2% HOPD). In multivariable analyses, ACDFs performed in an ASC (versus HOPD) were associated with 9.8% higher immediate procedure reimbursements (95% CI:7.5-12.2%), 17.2% higher patient out-of-pocket expenditures (95% CI:11.8-22.8), and 11.7% higher surgeon reimbursements (95% CI:9.18-14.2; all P<0.01) (all P<0.001). Surgery setting utilization varied by region, insurance-related factors, comorbidities, and procedural complexity. ConclusionsWe found that ASCs had significantly higher reimbursements compared to HOPDs. Regional variations in ASC utilization imply there are opportunities for standardization of care.