The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework has become the global standard for rating evidence certainty and grading strength of health-care recommendations in systematic reviews, clinical practice guidelines (CPGs), and health technology assessments (HTAs). However, as the methodology has evolved, its growing complexity and difficulties navigating the many articles providing GRADE guidance have created challenges for users. Moreover, GRADE guidance has been published across multiple journals and platforms, resulting in a body of work with considerable redundancy, modifications, and out-of-date material that requires meticulous appraisal of GRADE writings to identify and implement current guidance. In response, a group of GRADE methodologists developed Core GRADE, a simple yet comprehensive framework focused on the essential elements required to apply GRADE to paired comparisons of interventions. Building on prior GRADE publications, the authors reviewed existing guidance and distilled its fundamental components. This proposal represents an independent approach and has not received formal endorsement from the GRADE working group. During this process, they identified multiple areas where clearer recommendations were warranted and incorporated these improvements into the seven Core GRADE papers. This article presents the resulting innovations introduced by core GRADE, that include the use of flow charts and algorithms to guide GRADE implementation; an emphasis on viewing both individual GRADE domains and overall certainty as continua; and clarification of decisions related to addressing potential relative and absolute subgroup effects when formulating patient population, intervention, comparison, and outcome questions. PLAIN LANGUAGE SUMMARY: The GRADE framework was introduced in 2004 to help researchers and health-care professionals assess the certainty (quality) of evidence in systematic reviews and the strength of recommendations in CPGs and HTAs. Over the past 2 decades, it has become overwhelmingly the most widely used approach to making certainty of evidence and strength of recommendation decisions. However, many users now find GRADE increasingly complex, and guidance has appeared in numerous journals and platforms. This has created overlap, outdated information, and inconsistencies that make it difficult to identify the most current best approaches. To address these challenges, GRADE experts developed Core GRADE, a simplified but comprehensive version of GRADE. Core GRADE brings together the essential elements needed to apply GRADE when comparing health-care interventions (1 intervention vs 1 comparator). In addition to this simplification, Core GRADE offers several innovations. These include practical flowcharts and algorithms to guide step-by-step application of the framework; a new emphasis on viewing both individual domains and overall certainty of evidence as continua; and clearer advice on how to address different subpopulations when formulating research questions. Beyond simplification, these innovations further enhance GRADE's usefulness and ease of use.