OBJECTIVES: XLH is a rare genetic disorder in which low serum phosphorus levels lead to defective bone mineralization and consequently to rickets in children and osteomalacia in adults. Research concerning the patient experience of XLH is lacking. This qualitative interview study was conducted to address this gap in published literature and to evaluate the face and content validity of the Western Ontario McMaster Universities Osteoarthritis Inventory (WOMAC®) and Brief Pain Inventory–Short Form (BPI-SF) for use as endpoints in adult XLH clinical trials. METHODS: Face-to-face, semi-structured interviews were conducted with 18 adults with XLH in the US. Open-ended questioning was used to elicit spontaneous concepts relevant to the patient experience of XLH, focusing on the symptoms and functional limitations associated with the disease. Cognitive debriefing of the WOMAC® and BPI-SF was also conducted to assess the relevance of items and patient understanding of item wording, recall period, and response options. RESULTS:  Thirty-two distinct symptom concepts were elicited including pain symptoms, systemic symptoms, sensory symptoms, tiredness/fatigue symptoms, and musculoskeletal symptoms. Participants reported experiencing significant bone and joint pain, stiffness, mobility limitations, and an impact on their ability to work due to symptoms. A conceptual mapping exercise indicated that the key symptom and impact concepts reported by patients are assessed by the BPI-SF and WOMAC®, confirming their relevance to XLH patients. This was supported by the cognitive interviewing which found both instruments to be relevant and well understood by the majority of patients. CONCLUSIONS:  These interviews generated rich, qualitative insight into the patient experience of XLH. There was strong support for the face and content validity of the BPI-SF and WOMAC®, suggesting both instruments are suitable as XLH clinical trial endpoints with respect to these aspects of validity. Psychometric evaluation is recommended to establish the reliability, validity, and ability to detect change of these instruments.