The aim of this research was to determine cytologi- cal changes in wearers of acrylic-based complete den- tures. The study was conducted at the Prosthodontics Clinic in the Clinical Dental Center of the University Clinical Center of Kosovo (UCCK). The study included an experi- mental group (EG) and a control group (CG). Samples for cytological analysis were taken from oral mucosa areas in close contact with the denture base from both groups. The samples were analyzed in the pathology laboratory. Statistical data were analyzed using descriptive statistics and values expressed in percentages. A high keratinization index was recorded in the EG, while no keratinization was found in the CG. The picnotic and eosinophilic indexes were either not found at all or were low. Granular debris in 58.0% of the EG had low presence, moderate in 30.0%, and considerable in 8.0%. A low number of granulocytes were found in 68% of the EG, and a moderate presence in 34.0%. In 88% of the CG and 86% of the EG, erythrocytes were not found to be present. A weak presence of bacterial flora was recorded in 64.0% of the CG and 82% of the EG. Epithelial cells were recorded in both CG and EG at 60.0%. Parabasal cells were not found to be present in 96.0% of the CG and 100.0% of the EG. The presence of interstitial cells was significantly present in 100.0% of the CG and 94% of the EG. The wearing of complete dentures manifests with keratinous changes in oral mucosa. To control these changes, it is necessary to alter patients’ oral hygiene practices, focusing on cleaning and disinfecting the dentures, removing them for 24 hours during the night or even during the day for intervals of 6 to 8 hours within a day.