The study analyzed independent risk factors for transfusion-related adverse events (TrAEs) in 2028 TrAE patients and 336 reaction-free controls at a tertiary care hospital as of January 20, 2002. TrAE patients had older age, more prior transfusions, and more frequent hypertension, diabetes mellitus, cardiovascular disease, and malignancy (P < 0.05). Patients in the internal department had a higher risk compared to other departments (P < 0.05) and a larger volume of transfusion. One hour after transfusion, they had higher temperature, heart rate, respiratory rate, systolic pressure, white blood cell count and C-reactive protein, lower hemoglobin (P < 0.05). They used more antipyretics, corticosteroids, were in the ICU more often and had a longer hospital stay (P < 0.05). Multivariate logistic regression confirmed older age, more previous transfusions, hypertension, cardiovascular disease, malignancy and larger volume of transfusion as independent risk factors (P < 0.05). Better monitoring and tailored transfusion strategies are recommended for patients at risk.