Objective: The objective of the study is to develop a pragmatic tool to prioritize clinical guideline (CG) questions for updating, the UpPriority tool. Study Design and Setting: The development of this tool consisted of the following: (1) establishment of the working group, (2) generation of the initial version, (3) optimization of the tool (including an initial feasibility test, semistructured interviews, Delphi consensus survey, second feasibility test, external review, and pilot test), and (4) approval of the final version. Results: A total of 87 participants including methodologists, clinicians, and other relevant stakeholders contributed to the development of the UpPriority tool. The tool consists of six items: (1) impact of outdated recommendations on safety, (2) availability of new relevant evidence, (3) context relevance of the clinical question, (4) methodological applicability of the clinical question, (5) user's interest, and (6) impact on access to health care. The UpPriority tool includes detailed guidance for using the tool and rating each item (using a 7-point Likert scale), for calculating and ranking the questions, and for summarizing results. Conclusion: The UpPriority tool could be useful for standardizing prioritization processes when updating CGs and for fostering more efficient use of resources in the CG field.