Objectives: The purpose of this study was to evaluate the prevalence of denture-related oral mucosal lesions (DML) in São Francisco sertão microregion, in Sergipe State, Northeastern Brazil. Study Design: Data related to gender, age, type of denture, length of denture use, hygiene care, nocturnal denture wear, symptoms, and presence of DML were obtained. Statistical analysis included the Pearson's chi-square and multivariate logistic regression. Results: The global prevalence of DML was 50%, with a significant association between the DML and female gender, age ≥ 40 years, and length of use ≥ 5 years. By using the interaction model of logistic regression it was observed that females over 40 years have 4.5 greater odds of developing DML compared to males of the same age group. The DML more common was the type 2 denture stomatitis, followed by type 1 denture stomatitis and inflammatory fibrous hyperplasia. Conclusions: This study shows that the DML are more common in female over 40 years of age, suggesting that hormonal chances and age-related factors may favor the development of lesions. In addition, there is a significant association between length of denture use and prevalence of DML.