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BACKGROUND Prior reports of positive associations between edentulism and all-cause mortality have been limited by onetime assessments of edentulism and inadequate control of known confounding variables. The authors aimed to assess the association between edentulism and mortality using a longitudinal clinical oral health cohort. METHODS The authors used data from the Department of Veterans Affairs Dental Longitudinal Study, an ongoing, closed-panel cohort study from 1968 through 2019 (N = 1,229). Dentition status was evaluated through triennial clinical examinations. Mortality was assessed via the National Death Registry. The authors used Cox regression models to estimate the association between edentulism and all-cause mortality after covariate adjustment. Furthermore, the authors calculated propensity scores and assessed hazard ratios (HRs) in a trimmed, matched, and inverse probability weighted sample. RESULTS Participants who were edentulous (N = 112) had 1.24 (95% CI, 1.00 to 1.55) times the hazard of all-cause mortality compared with those who were nonedentulous, after adjustment with time-varying covariates. Use of propensity scores in the model resulted in slightly elevated HRs compared with the standard Cox model, regardless of propensity score method; adjusted HRs were 1.35 (95% CI, 1.01 to 1.80) after matching, 1.26 (95% CI, 1.00 to 1.59) after trimming, and 1.29 (95% CI, 1.18 to 1.42) after inverse probability weighting. CONCLUSIONS Edentulism was associated with an increased risk of all-cause mortality in a cohort that captured incident edentulism. This association was consistent after multiple methods to account for confounding. PRACTICAL IMPLICATIONS The findings of this study suggest that edentulism is associated with an increase in risk of mortality, after accounting for salient confounding variables using multiple approaches. Efforts to improve equitable access to tooth-preserving treatments are critical.