Background: This study aimed to investigate the effect of metabolic syndrome (MetS) on tooth loss in adults from a population-based sample. Methods: Cross-sectional analysis based on data from a cohort study (2009 to 2014) with adults from Southern Brazil. MetS (exposure), lack of functional dentition and number of lost teeth (outcomes) were assessed using self-reported, laboratory and clinical data. Possible confounders included sex, age, family income, education level, smoking status, and sugar consumption. The effect of MetS on the outcomes was estimated using conventional logistic or negative binomial regression models. Marginal structural modeling (MSM) with stabilized weights (a counterfactual analytical method) was also used to enhance group comparability and estimate causal effects. Results: A total of 1,283 participants had available information for the outcomes. Individuals with MetS were more likely to experience a lack of functional dentition than those without MetS (odds ratio [OR] from logistic regression, 1.7; 95% CI, 1.0 to 2.9; OR from MSM, 3.2; 95% CI, 2.3 to 4.6). Moreover, the number of teeth lost was 20% higher in participants with MetS compared with those without MetS in conventional analysis (mean ratio [MR], 1.2; 95% CI, 1.1 to 1.3). The MR increased to 1.7 (95% CI, 1.5 to 2.0) when using MSM. Conclusion: Our findings provide evidence on the effect of MetS on tooth loss.