PURPOSE: When carrying out prosthetic rehabilitation of edentulous and partially edentulous patients, great attention is paid to the personal attitude of the patients, their satisfaction with oral health and psychosocial interaction due to tooth loss, as well as the treatment of the resulting disorders. This attention has led to the development of various instruments for examining the quality of life related to oral health. The aim of this study was to develop and validate a reliable instrument in the Serbian language suitable for measuring oral health-related quality of life in patients who have been rehabilitated with complete or partial dentures. Мaterials and Methods: The study was unicentric and cross-sectional, and assessed the reliability and validity of a newly developed instrument for measuring the oral health-related quality of life in denture wearers (OHRQoL-DW). It was conducted on a sample of 200 adults from Serbia, wearers of various types of dentures, with a mean age 66.9 ± 10.3 years and male/female ratio of 86/114 (43%/57%). RESULTS: The definitive version of the OHRQoL-DW scale with 28 items showed very good reliability, with Cronbach's alpha = 0.938. Good temporal stability of the questionnaire was demonstrated, and satisfactory results were obtained for divergent and convergent validity tests. Exploratory factorial analysis revealed four domains of oral health-related quality of life in denture wearers: physical, psychosocial, environmental and aesthetic. CONCLUSIONS: The OHRQoL-DW scale is a reliable and valid generic instrument for measuring the oral health-related quality of life in patients wearing dentures, which is one of the most important outcomes of oral health in prosthetic treatment.