Fluoride is often referred to as a double-edged sword, as insufficient intake is associated with dental caries; excessive intake leads to dental and skeletal fluorosis. The toxic effects of fluoride can be classified as acute and chronic. The acute toxicity of fluoride occurs after a single ingestion of a large amount of fluoride. On the other hand, the chronic toxicity of fluoride is caused by long-term ingestion of the chemical element. Skeletal fluorosis is the result of chronic fluoride toxicity. Fluorosis is an endemic disease in several geographic areas of several countries, including the Rift Valley region of Ethiopia. Nevertheless, there are few epidemiological data on skeletal fluorosis. This study was initiated to determine the prevalence of skeletal fluorosis among adults in the Rift Valley region of Ethiopia. A single-point cross-sectional prevalence study was conducted between January 2023 and February 2023 to determine the prevalence of skeletal fluorosis in adults who met the inclusion criteria. Radiologic, biological (serum and urinalysis), and physical examinations were performed to collect the required data. Physical examinations included assessments of Range of Motion (RMO), muscle strength, and dermatomes of the upper and lower extremities' major joints, muscles, and nerve roots. In addition, the stress tests developed by Susheela and Bhatnagar [1] were used as part of the physical examination to diagnose the disease. After analyzing the musculoskeletal, radiological and biological data of the 42 study participants, the prevalence of skeletal fluorosis was calculated to be 21.4% (n=9). This prevalence rate indicates the importance of immediate intervention, including defluoridation and public education.