Introduction: Quality of life (QOL) in chronic limb-threatening ischemia (CLTI) is critical to comprehensive outcomes analysis and provision of high-value care. This PhD thesis aims to develop a blueprint for a new CLTI-specific QOL measurement instrument that does not currently exist. The PhD experience from a consultant’s perspective is also provided which is unique in Victoria. Methods: The instrument blueprint was developed by demonstrating the need, defining the purpose, developing a conceptual model, and identifying item content. A wide range of research methodologies was employed according to contemporary standards of QOL instrument development. This included a rigorous evidence synthesis of QOL instruments, data, and applications, to provide a prospectively designed framework for the QOL instrument. Results: There were six key components of the blueprint. Firstly, defining a predictive CLTI-specific QOL instrument. Secondly, a multidisciplinary team comprising healthcare professionals and patients was assembled. Thirdly, outlining ideal measurement properties, summary scores, and capturing all disease states. Fourthly, the importance of a feasible instrument with low responder and administrative burden, and simplicity of scoring and interpretation was highlighted. Fifthly, showing how clinical utility was important for implementation, with an emphasis on minimal clinically important difference and prognostic models. Finally, QOL in CLTI is related to themes involving independence, identity, coping, and not being alone. Conclusion: A blueprint for the new CLTI-specific QOL instrument has been developed to be fit for purpose in CLTI. The research methodologies employed are foundational in vascular surgery. The instrument will help to improve the quality and sustainability of care we provide to patients. This PhD will also help to develop the academic landscape of vascular surgery in Victoria.