Thrombocytopenia is a common condition in several populations of hospitalized patients, including those with hematological and solid tumor cancer,1, 2 those with chronic liver disease,3 and critically ill neonates4 and adults,5 and it has been associated with increased rates of bleeding, transfusion requirements, and mortality.6-9 Prophylactic platelet transfusions are often recommended in patients with severe thrombocytopenia, but the supporting evidence is primarily derived from trials in hematological patients10-12 and clinical practice varies considerably.13-15 Prior to prophylactic platelet transfusion, the risk of bleeding and the beneficial effects of transfusion must be viewed in light of the potentially harmful effects, which, although rare, include serious and potentially life-threatening reactions, such as anaphylaxis, transfusion-transmitted infections, and transfusion-related acute lung injury.16 Harm from platelet transfusions has been observed in randomized clinical trials (RCTs) among preterm infants17 and patients with intracerebral hemorrhage.18 Therefore, we aimed to assess the benefits and harms of prophylactic platelet transfusions versus no prophylaxis on patient-important outcomes in hospitalized patients with thrombocytopenia. We hypothesized that the evidence base for non-hematological patients would be sparse and uncertain.