Despite concerns about potential side effects, based both on historical experience with plasma products and more recent concerns about contemporary use of plasma, COVID-19 convalescent plasma has been shown to be a very safe product. Research early in the COVID-19 pandemic documented-among the very large population of convalescent plasma recipients in the US Convalescent Plasma Study component of the FDA-authorized Expanded Access Program-that the overall risk profile was no different than that seen for fresh frozen plasma, a product used routinely in medical practice. The safety of CCP was further demonstrated using real-world evidence, pragmatic trials, and formal randomized trials. The rates of all serious adverse events were very low, an especially impressive finding in light of the fact that nearly all safety data came from the use of COVID-19 convalescent plasma in patients who were hospitalized, were older, and/or had significant co-morbid cardiopulmonary and metabolic disorders. The well-known complications of blood and plasma transfusions-transfusion-associated circulatory overload and transfusion-related acute lung injury-were found with no higher incidence than with standard use of blood and plasma, nor was there evidence for antibody-dependent enhancement or increased incidence of thromboembolic events. The comprehensive safety profile derived from studies enrolling hundreds of thousands of recipients of COVID-19 convalescent plasma across the world should allay safety fears about the rapid deployment of convalescent plasma in future pandemics.