A 72-year-old woman, who had been in the hospital for treatment of right leg cellulitis for two days, suddenly developed increasing SOB with worsening heart failure (HF) 6 hours after a blood transfusion of 2 units packed cells for chronic anemia (Hb 7.8 mg%) (Chest X-ray 1 and Chest X-ray 2). PMH was significant for chronic HF relating to hypertensive cardiomyopathy, chronic atrial fibrillation (AF), and end-stage renal disease (ESRD), presumably nephrosclerotic (BUN 125 mg/mL, Cr 8.8 mg/mL, and eGFR 5 ml/hr). Physical findings were consistent with biventricular HF- PMI displaced to the left, RV and LV lifts, a Gr 2/6 systolic murmur at the apex and left sternal border, loud S3 gallop, and bilateral crackles at both lung fields. BT measured 38.1°C, BP 177/84 mmHg, PR 130/min, irregular, and RR 20/min. Jugular veins were distended with JVP measured 10 cm H2O. In addition to cellulitis of the right leg, there was 4+ pitting edema in both legs. Corresponding to the worsening HF incurred after blood transfusion, there was newly developed ST depression with T wave inversion in II, III, and aVF. Additionally, there was a rightward shift of the QRS axis (from +74° to +95°) alongside a more clockwise heart rotation with more extent of slow R progression in the precordial leads (ECG 1 before and ECG 2 after blood transfusion). After ruling out acute myocardial infarction (MI) and pulmonary embolism (i.e., no elevation of cardiac enzymes and D-dimer in serial blood sampling), the ECG changes were attributed to blood transfusion-induced volume overload, which resulted in the worsening of HF.