To evaluate the frequency of maxillary dentures-related lesions and the possible associated risk factors. Ninety-seven participants were selected, and a complete anamnesis, physical examination and tests of occlusion vertical dimension (OVD), retention and stability of the denture, biofilm quantification, cytopathology, sialometry, pH analysis and buffer capacity of the saliva were performed. Statistical analyses were performed with the Pearson?s chi-square, Mann-Whitney tests, and Pearson?s coefficient (p<0.05). In 78% of the participants at least one denture-related lesion was found. Denture-associated stomatitis (63%), inflammatory fibrous hyperplasia (19%) and traumatic ulceration (11%) were the 3 most frequent lesions. The habit of night use of the denture was considered an independent risk factor for the development of oral lesions [OR=3.0 (95% CI 1.09-8.56); p<0.05]. Furthermore, the longest period of use of the same denture and biofilm also had statistically significant relation to oral lesions. The biofilm seems to be more related to the prevalence of oral lesions according to the multiple logistic regression [OR=1.3 (95% CI: 1.01-1.83) p<0.05]. The lack of a dentures? cleaning solution and detrition of the prothesis were independent risk factors for denture-associated stomatitis. Male gender, loss of OVD and bad buffer capacity were risk factors for angular cheilitis. Fractures of the base and repair of broken dentures were risk factors for traumatic ulcers. These results show a high frequency of denture-related lesions. Besides, participants hygiene habits and poor quality of the dentures were the main factors for the development of these lesions.