To compare survival outcomes between patients with poorly differentiated versus well-differentiated glottic squamous cell carcinoma (GSCC). Fifty-five patients with well-differentiated newly diagnosed GSCC were pair-matched to 55 patients with poorly differentiated GSCC according to age, sex, year of diagnosis, overall stage, treatment (surgery type, neck dissection, surgical margin, and chemoradiation), smoking, and alcohol use. Survival analysis was performed using Kaplan-Meier estimates, and matched-pair survival was estimated using the Cox proportional hazards regression model. Patients with well-differentiated GSCC had significantly better overall survival (OS) (P = 0.001), disease-specific survival (DSS) (P < 0.001), and disease-free survival (DFS) (P = 0.003) than patients with poorly differentiated GSCC. Moreover, matched-pair analysis indicated that increased differentiation was associated with a significantly reduced risk of overall death (HR, 0.18; 95% confidence interval [CI], 0.07-0.46), death owing to disease (HR, 0.16; 95% CI, 0.05-0.45), and disease recurrence (HR, 0.17; 95% CI, 0.07-0.41), and these risks were reduced approximately 4-fold, 3.7-fold, and 9-fold, respectively, after adjustment for cancer-associated variables. Survival differed significantly between the well-differentiated and poorly differentiated GSCC patients after adjustment for cancer prognosis-associated variables. Thus, identifying potential differences in the molecular characteristics between these two groups of patients would help to further stratify these patients and ensure appropriate individualized treatment decisions. Basing treatment strategies on the level of differentiation may improve survival.