BACKGROUND CONTEXT: Vertebral fragility fractures (VFFs), mostly due to osteoporosis, are very common and are associated with significant morbidity and mortality. There is a lack of consensus on the appropriate management of patients with or suspected of having a VFF. PURPOSE: This work aimed at developing a comprehensive clinical care pathway (CCP) for VFF. STUDY DESIGN/SETTING: The RAND/UCLA Appropriateness Method was used to develop patient-specific recommendations for the various components of the CCP. The study included two individual rating rounds and two plenary discussion sessions. METHODS: A multispecialty expert panel (orthopedic and neurosurgeons, interventional [neuro]radiologists and pain specialists) assessed the importance of 20 signs and symptoms for the suspicion of VFF, the relevance of 5 diagnostic procedures, the appropriateness of vertebral augmentation versus nonsurgical management for 576 clinical scenarios, and the adequacy of 6 aspects of follow-up care. RESULTS: The panel identified 10 signs and symptoms believed to be relatively specific for VFF. In patients suspected of VFF, advanced imaging was considered highly desirable, with MRI being the preferred diagnostic modality. Vertebral augmentation was considered appropriate in patients with positive findings on advanced imaging and in whom symptoms had worsened and in patients with 2 to 4 unfavorable conditions (eg, progression of height loss and severe impact on functioning), dependent on their relative weight. Time since fracture was considered less relevant for treatment choice. Follow-up should include evaluation of bone mineral density and treatment of osteoporosis. CONCLUSIONS: Using the RAND/UCLA Appropriateness Method, a multispecialty expert panel established a comprehensive CCP for the management of VFF. The CCP may be helpful to support decision-making in daily clinical practice and to improve quality of care.