OBJECTIVES: To evaluate the influence of facility case-volume on survival in patients with locally advanced papillary thyroid cancer (PTC), and to identify prognostic case-volume thresholds for facilities managing this patient population. STUDY DESIGN: Retrospective database study. METHODS: The 2004-2017 National Cancer Database was queried for patients receiving definitive surgery for locally advanced PTC. Using K-means clustering and multivariable Cox proportional-hazards (CPH) regression, two groups with distinct spectrums of facility case-volumes were generated. Multivariable CPH regression and Kaplan-Meier analysis assessed for the influence of facility case-volume and the prognostic value of its stratification on overall survival (OS). RESULTS: Of 48,899 patients treated at 1304 facilities, there were 34,312 (70.2%) females and the mean age was 48.0 ± 16.0 years. Increased facility volume was significantly associated with reduced all-cause mortality (HR 0.996; 95% CI, 0.992-0.999; p = 0.008). Five facility clusters were generated, from which two distinct cohorts were identified: low (LVF; <27 cases/year) and high (HVF; ≥27 cases/year) facility case-volume. Patients at HVFs were associated with reduced mortality compared to those at LVFs (HR 0.791; 95% CI, 0.678-0.923, p = 0.003). Kaplan-Meier analysis of propensity score-matched N0 and N1 patients demonstrated higher OS in HVF cohorts (all p < 0.001). CONCLUSIONS: Facility case-volume was an independent predictor of improved OS in locally advanced PTC, indicating a possible survival benefit at high-volume medical centers. Specifically, independent of a number of sociodemographic and clinical factors, facilities that treated ≥27 cases per year were associated with increased OS. Patients with locally advanced PTC may, therefore, benefit from referrals to higher-volume facilities. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:443-450, 2023.