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The normative role of the World Health Organization (WHO) involves creating evidence-based, principled guidelines to guide its Member States in making well-informed public health decisions. While these guidelines often need to be adapted to ensure contextual relevance, foster better implementation and adherence, adapting existing guidelines is more efficient than creating new ones. Here we describe the adaptation of the WHO coronavirus disease 2019 (COVID-19) living guideline on pharmacological interventions for the Caribbean using the grading of recommendations, assessment, development and evaluation (GRADE)-ADOLOPMENT method. The Caribbean Public Health Agency and the Pan American Health Organization led the effort, assembling a diverse panel of 16 experts from seven Caribbean countries and territories. The adaptation process, involving 15 steps, was guided by an experienced methodologist and included selecting relevant clinical questions and prioritizing them based on regional needs. The panel evaluated the latest WHO guidelines and integrated additional local data. They adjusted the direction and strength of several recommendations to better fit the Caribbean context, considering local values and preferences, resources, accessibility, feasibility and impact on health equity. Ultimately, we changed the direction of two recommendations and the strength of five, tailoring them to regional realities. This effort highlights the importance of adapting global guidelines to local settings, improving their applicability and effectiveness. The adaptation process also serves as a valuable opportunity for skill transfer and capacity-building in guideline development. Continued research is needed to assess the impact of these adaptations on health-care outcomes in the Caribbean., ((c) 2024 The authors; licensee World Health Organization.)