Objective: To develop evidence-based clinical practice recommendations regarding transfusion practices in non-bleeding, critically ill adults. Design: A task force involving 13 international experts and three methodologists used the GRADE approach for guideline development. Methods: The task force identified four main topics: red blood cell transfusion thresholds, red blood cell transfusion avoidance strategies, platelet transfusion, and plasma transfusion. The panel developed structured guideline questions using population, intervention, comparison, and outcomes (PICO) format. Results: The task force generated 16 clinical practice recommendations (3 strong recommendations, 13 conditional recommendations), and identified five PICOs with insufficient evidence to make any recommendation. Conclusions: This clinical practice guideline provides evidence-based recommendations and identifies areas where further research is needed regarding transfusion practices and transfusion avoidance in non-bleeding, critically ill adults.