OBJECTIVES: Fibrodysplasia Ossificans Progressiva (FOP) is a rare and disabling genetic condition of progressive extraskeletal bone formation. Physical functioning declines as FOP progresses. The objective was to develop a measure of physical function (PF) in adults with FOP. METHODS: We reviewed the PROMIS PF item bank for relevant items for FOP, and 44 PF items were identified.  We then conducted concept elicitation (CE) interviews in 21 patients diagnosed with FOP (with varying levels of disease severity) who attended the International FOP Association meeting.  The selected PF items were administered after the CE interviews.  Interview data were analyzed to identify categories of physical functioning that were impacted by FOP. Based on the CE findings and PF item data, 26 items were initially selected for the new measure.  Clinical experts in FOP reviewed the proposed set of items. Five additional items were incorporated into the draft measure, and cognitive interviews (CIs) were conducted in 10 patients, and revisions were made to the final FOP-PF Questionnaire (FOP-PFQ; 28 items). RESULTS: For the CE interviews, mean age was 30 years (range 16–54) and 58% were female. For the CIs, mean age was 31 years (range 16–57) and 50% were female. CE interviews demonstrated substantial impacts of FOP on mobility, upper extremity function, and related activities.  The CE findings, PROMIS PF item descriptive data, and discussion with clinical experts resulted in 31 relevant items which were included in the draft FOP-PFQ. Based on the CIs, the majority of patients understood the instructions, questions, and response scales; three items were deleted due to redundancy or item removal from the original PROMIS item bank. CONCLUSIONS: This qualitative research supports the content validity of the FOP-PFQ and illustrates the application of PROMIS item banks for efficient new instrument development in an ultra-rare and disabling genetic disease.