ObjectivesTo determine whether tooth loss affects all-cause and cause-specific mortality in a nationally representative sample of adults with diabetes mellitus (DM) in the United States. MethodsThis prospective cohort study involved 8207 participants aged 30 years or older at baseline, all diagnosed with diabetes mellitus and enrolled in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Tooth loss was stratified into 28 teeth (complete), 20–27 teeth (tooth loss), 9–19 teeth (lacking functional), 1–8 teeth (severe tooth loss) and edentulism. To estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for all-cause and specific-cause mortality in diabetes mellitus participants according to tooth loss, multivariate cox proportional hazards regression models were used. Relationships between mortality and quartiles of mean tooth loss levels were analyzed, with the lowest quartile as the baseline for comparisons. ResultsDuring a median of 6.92 years of follow-up, 2317 deaths were documented. After multivariate adjustments, higher tooth loss levels were significantly and non-linearly associated with higher risks of all-cause, CVD-related and DM-related mortality among participants with DM. When compared with the reference group of mean tooth loss levels, the highest quartile showed significantly increased risks: all-cause mortality (HR, 2.11; 95 % CI, 1.53–2.91, P-trend < 0.001), CVD-related mortality (HR, 3.24, 95 % CI, 1.54–6.85, P-trend < 0.001) and DM-related mortality (HR, 2.78, 95 % CI, 1.15–6.68, P-trend < 0.001). ConclusionsTooth loss is associated with an increased risk of all-cause, CVD-related and diabetes mellitus mortality among adults with diabetes mellitus in the US. Clinical SignificanceThis study presents evidence for physicians and dentists that higher tooth loss was significantly associated with increased risk of all-cause, CVD-related and diabetes mellitus mortality in a dose-response manner among adults with diabetes mellitus. Therefore, assessment of survival in individuals with diabetes mellitus could pay attention to the tooth loss.