Objective: Drug reaction with eosinophilia with systemic symptoms (DRESS) syndrome is a life threatening hyperactivation of immune system by relevant drug use. Lethality accounts up to 10% of all patients. Herein, we present a successful treatment of a DRESS syndrome which complicated with end-stage renal disease, liver dysfunction, eosinophilia, congestive heart failure, skin rash and severe systemic symptoms. Design and method: Fifty-six- year-old Japanese woman was admitted to our hospital for the treatment of duodenal tumor by endoscopic submucosal dissection which accidentally caused perforation. She was treated by piperacillin tazobactam and acetoaminophen. Although the intraperitoneal abscess was cured, she had developed end-stage renal disease, liver dysfunction, eosinophilia, congestive heart failure, skin rash and severe systemic symptoms with high fever of 40 degrees Celcius and tachycardia. Plain CT scan showed kidney enlargement and gallium scintigraphy showed increased accumulation in the bilateral kidneys. eGFR declined to 12 ml/min/1.73m2 from the baseline of 75 and urine tubular makers were elevated. RegiSCAR score was six, and we diagnosed this case as DRESS syndrome. Drug-induced lymphocyte stimulation test turned out positive for both piperacillin tazobactam and acetoaminophen. Results: We decided to administer corticosteroids for the treatment of severe organ involvement. After 30 milligrams of intravenous prednisolone (0.6 mg/kg/day), the above symptoms subsided immediately without causing any adverse effects. The corticosteroids were tapered carefully because it is known that autoimmune disorders such as reactive arthritis, systemic lupus erythematosus and autoimmune hemolytic anemia could develop during the treatment course. The patient's renal function recovered to eGFR of 60 without induction of dialysis. After 12 months of treatment, the patient is free of corticosteroids without any relapse of DRESS syndrome. Conclusions: DRESS syndrome could be caused by a series of drugs, and could be a lethal disease. Immediate diagnosis and treatment are required for acceptable prognosis. Careful follow up should be made because of the relapses, reactivation of viruses such as cytomegaro virus and HHV-6, and autoimmune complications.