OBJECTIVES: Post-transfusion purpura (PTP) is a rare but serious transfusion complication presenting as severe thrombocytopenia with hemorrhage (e.g., intracranial, gastrointestinal). The study objectives were to assess PTP occurrence and potential risk factors among inpatient Medicare beneficiaries, ages 65 and older, during 2011-2018. METHODS: This retrospective claims-based study utilized Medicare databases. Blood transfusions were identified by procedure and revenue center codes, and PTP via diagnosis codes. PTP rates (per 100,000 transfusion stays) were evaluated overall, by calendar year, demographics, immunocompromised (IC) status, blood components and units transfused. Fisher’s exact tests were performed to compare PTP rates, and Cochran-Armitage tests assessed trends over time, by age and transfusion volume. RESULTS: Among 10,529,555 inpatient transfusion stays, 215 had a PTP diagnosis recorded, a rate of 2.0 per 100,000 stays, with annual rates ranging from 1.6 in 2011 to 2.9 in 2018 (p<0.001). The highest PTP rates by blood component groups were: platelets only (8.3), platelets and plasma (12.1), RBCs and platelets (14.2), and RBCs, plasma and platelets (14.6). PTP rates for males vs. females were 2.3 and 1.9 (p=0.15); and for whites vs. non-whites were 1.9 and 2.5 (p=0.12). Rates for ages 65-69, 70-74, 75-79, 80-84, and ≥85 were: 2.5, 2.6, 2.0, 2.0, and 1.3, respectively (p=0.003). PTP rates by number of units transfused were: 1.3 for 1 unit, 1.1 for 2-4 units, 4.1 for 5-9 units, and 8.2 for >9 units (p<0.001). Among IC beneficiaries PTP rate was 3.8 vs. 1.6 for non-IC [rate ratio 2.3 (95%CI 1.7-3.1)]. CONCLUSIONS: Our population-based study is the largest-to-date and shows increasing PTP risk over time and with greater number of units transfused. The study identified significantly higher PTP risk in IC beneficiaries and with platelet transfusion(s). Our investigation suggests a decline in PTP risk with advancing age and variations in risk by sex and race, which need further research.