Purpose: This study investigated the association between health status and tooth loss based on data from the National Health Insurance Service-Health Examinee Cohort in 2002-2015. Methods: Multivariate Cox proportional hazards regression analyses were applied to a longitudinal retrospective database, which was updated and newly released in 2018, to assess the association between health status and tooth loss while adjusting for potential confounders among sociodemographic and economic factors (sex, age, household income, insurance, and presence of disability), general and oral health status (body mass index [BMI], smoking and drinking status, periodic dental visits and scaling, and brushing before sleep), and comorbid disease (hypertension, diabetes mellitus [DM], and Charlson comorbidity index [CCI]). Results: Among 514,866 participants from a South Korean population, 234,247 (45.5%) participants satisfying the inclusion criteria were analyzed. In the adjusted multivariate analysis, sex, age, household income, insurance, presence of disability, BMI, smoking and drinking status, periodic scaling, tooth brushing before sleep, DM, and CCI showed statistically significant associations with the loss of at least 1 tooth. The risk of experiencing a loss of ${\geq}4$ teeth was associated with an increase in age (in those 50-59 years of age: hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.93-2.03; in those 60-69 years of age: HR, 2.93; 95% CI, 2.85-3.02; and in those 70-79 years of age: HR, 2.93; 95%, CI 2.81-3.05), smoking (HR, 1.69; 95% CI, 1.65-1.73), and DM (HR, 1.43; 95% CI, 1.38-1.48). Conclusions: The results of this study showed that the risk of experiencing tooth loss was related to multiple determinants. DM and smoking were especially significantly associated with tooth loss.