BACKGROUND: Alpha-gal syndrome (AGS) is caused by IgE antibodies against the alpha-gal oligosaccharide, which is structurally similar to the Group B antigen. Recent case reports of severe allergic transfusion reactions (ATRs) in Group O patients receiving Group B plasma and platelets raise the possibility of a new adverse event, herein called transfusion-related AGS (TRAGS). The primary goal of this study was to assess the frequency of Groups B and AB plasma and platelet transfusions to Group O patients. STUDY DESIGN AND METHODS: In this multi-site retrospective study, participating sites submitted the numbers of platelet and plasma transfusions administered during a 2-year period categorized by patient and product ABO group. RESULTS: Fourteen sites from 10 countries participated. Group O patients received Group AB for an average of 9.9% (range 2.8%-29.2%) of plasma transfusions and Group B for 3.2% (0%-12.8%). AB plasma transfusion to Group O patients represented 4.5% (0.9%-14.6%) of the total plasma transfused; Group B 1.4% (0%-5.1%). Group O patients received Group AB for an average of 1.5% (range 0%-5.9%) of platelet transfusions and Group B for 4.1% (0%-14.2%). AB platelet transfusion to Group O patients represented 0.6% (0%-2.7%) of the total platelets transfused; Group B platelets were 1.8% (0%-6.7%). DISCUSSION: Evidence supporting the possibility of a new adverse event, TRAGS, is accumulating. This study quantifies how often Group O patients may be exposed to Group B antigen in Group B or AB plasma and/or platelet transfusions, providing an estimate of the scope of potential risk for TRAGS.