Purpose To provide evidence-based guidance on the use of platelet transfusion in people with cancer. This guideline updates and replaces the previous ASCO platelet transfusion guideline published initially in 2001. Methods ASCO convened an Expert Panel and conducted a systematic review of the medical literature published from September 1, 2014, through October 26, 2016. This review builds on two 2015 systematic reviews that were conducted by the AABB and the International Collaboration for Transfusion Medicine Guidelines. For clinical questions that were not addressed by the AABB and the International Collaboration for Transfusion Medicine Guidelines (the use of leukoreduction and platelet transfusion in solid tumors or chronic, stable severe thrombocytopenia) or that were addressed partially (invasive procedures), the ASCO search extended back to January 2000. Results The updated ASCO review included 24 more recent publications: three clinical practice guidelines, eight systematic reviews, and 13 observational studies. Recommendations The most substantial change to a previous recommendation involved platelet transfusion in the setting of hematopoietic stem-cell transplantation. Based on data from randomized controlled trials, adult patients who undergo autologous stem-cell transplantation at experienced centers may receive a platelet transfusion at the first sign of bleeding, rather than prophylactically. Prophylactic platelet transfusion at defined platelet count thresholds is still recommended for pediatric patients undergoing autologous stem-cell transplantation and for adult and pediatric patients undergoing allogeneic stem-cell transplantation. Other recommendations address platelet transfusion in patients with hematologic malignancies or solid tumors or in those who undergo invasive procedures. Guidance is also provided regarding the production of platelet products, prevention of Rh alloimmunization, and management of refractoriness to platelet transfusion ( www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki ).