Importance: Platelet transfusion is a frequent procedure with benefits and risks. Objective: To provide recommendations in adult and pediatric populations in whom platelet transfusions are commonly performed. Evidence Review: Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was applied to findings from 21 randomized trials and 13 observational studies in contexts of limited randomized clinical trial data. Transfusion strategies using fewer (restrictive) vs greater (liberal) amounts of platelets were compared. Findings: Evidence demonstrated that restrictive transfusion strategies probably did not cause increases in mortality or bleeding relative to liberal strategies across predefined clinical populations. Exceedingly low incidence of spinal hematoma was identified in patients with thrombocytopenia undergoing lumbar puncture. Because definitions of restrictive strategies varied across trials, recommendations reflect practical guidance. The following recommendations are strong recommendations with high/moderate-certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding patients receiving chemotherapy or undergoing allogeneic stem cell transplant, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. For consumptive thrombocytopenia in neonates without major bleeding, platelet transfusion is recommended when platelet count is less than 25 × 103/μL. In patients undergoing lumbar puncture, platelet transfusion is recommended when platelet count is less than 20 × 103/μL. In patients with consumptive thrombocytopenia due to Dengue without major bleeding, platelet transfusion is not recommended. The following recommendations are conditional recommendations with low/very low-certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding adults undergoing autologous stem cell transplant or with aplastic anemia, prophylactic platelet transfusion is not recommended. In adults with consumptive thrombocytopenia without major bleeding, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing central venous catheter placement in compressible anatomic sites, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing interventional radiology, platelet transfusion is recommended when platelet count is less than 20 × 103/μL for low-risk procedures and less than 50 × 103/μL for high-risk procedures. For adults undergoing major nonneuraxial surgery, platelet transfusion is recommended when platelet count is less than 50 × 103/μL. For patients without thrombocytopenia undergoing cardiovascular surgery in the absence of major hemorrhage, including those receiving cardiopulmonary bypass, platelet transfusion is not recommended. For nonoperative intracranial hemorrhage in adults with platelet count greater than 100 × 103/μL, including those receiving antiplatelet agents, platelet transfusion is not recommended. Conclusions And Relevance: A consistent pattern of evidence supports the implementation of restrictive platelet transfusion strategies. Restrictive strategies reduce risk of adverse reactions, mitigate platelet shortages, and reduce costs. It is good practice to consider overall clinical context and alternative therapies in the decision to perform platelet transfusion.