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(1) Background: Cardiovascular disease (CVD) and edentulism are major public health challenges with shared risk factors and overlapping inflammatory pathways. (2) Methods: This study investigates the association between complete tooth loss and cardiovascular disease in a nationally representative sample of U.S. adults using data from the 2015–2018 National Health and Nutrition Examination Survey (NHANES). A cross-sectional analysis was conducted among adults aged ≥30 years, incorporating clinically assessed dental status and self-reported CVD outcomes. Weighted multivariate logistic regression models were conducted to investigate the relationship between complete edentulism and different cardiovascular conditions adjusted for age, sex, race/ethnicity, education, income, BMI, and diabetes status. 3) Results: Individuals with cardiovascular conditions, including coronary heart disease, heart attack, stroke, and congestive heart failure, had higher odds of complete edentulism compared to those without cardiovascular conditions, with odds ratios ranging from 1.60 to 1.85 (p < 0.01). Older age, lower educational attainment, and lower income were also associated with higher odds of tooth loss. (4) Conclusions: This study contributes further to the existing evidence of oral-systemic health link, showing that individuals with cardiovascular conditions are more likely to be edentulous.