OBJECTIVES: Acute infections following transfusion (AIFT) are serious transfusion-related complications which can result in fever, chills, sepsis, septic shock, and death. The study objective was to assess AIFT occurrence and potential risk factors among inpatient elderly Medicare beneficiaries, ages 65 and older, during 2012-2015. METHODS: This retrospective claims-based study utilized large Medicare databases for calendar years 2012-2015. Blood transfusions were identified by ICD-9-CM procedure and revenue center codes, whereas AIFT was ascertained via diagnosis code. Our study evaluated AIFT rates (per 100,000 inpatient transfusion stays) among elderly, overall and by calendar year, age, sex, race, blood components and number of units transfused. Fisher’s exact tests were performed to compare AIFT rates, and Cochran-Armitage tests were used to ascertain AIFT occurrence trends by calendar year, age, and transfusion volume. RESULTS: Among 7,899,680 inpatient transfusion stays for elderly beneficiaries during 2012-2015, 188 had an AIFT diagnosis recorded, an overall rate of 2.4 per 100,000 stays. AIFT rates by number of units transfused were: 1.6 for 1 unit, 2.1 for 2-4 units, 3.4 for 5-9 units, and 5.0 for >9 units (p<0.001). AIFT rates by blood component groups were: 2.0 for RBCs only, 1.1 for plasma only, 8.7 for platelets only, 3.1 for RBCs and plasma, 13.6 for RBCs and platelets, and 3.2 for RBCs, plasma and platelets. AIFT rates for age categories 65-69, 70-74, 75-79, 80-84, 85 and over were 2.8, 2.7, 2.5, 2.4, and 1.6, respectively (p=0.0173). Females and males had AIFT rates of 1.8 and 3.1, respectively (p<0.001). CONCLUSIONS: Our large population-based study shows significantly elevated AIFT risk with greater number of units transfused and suggests higher AIFT rates for platelet transfusions. The study also suggests potential effects of advancing age and gender on AIFT occurrence, which need further investigations. Study limitations include possible underrecording or misrecording of transfusion procedures, units, and diagnosis codes.