Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug reaction. Although the severity-of-illness score (SCORTEN) has been proposed for toxic epidermal necrolysis (TEN) for 10 years, a prognostic score for DRESS is still lacking. To identify prognostic factors of DRESS patients during hospitalization in one medical health system in Taiwan. We retrospectively reviewed all patients with DRESS diagnosed by dermatologists in Chang Gung Memorial Hospital (CMGH) Health System from 2001 to 2010. To study prognostic factors, we collected data at early disease and maximal disease stages. 91 individuals, including 13 dead patients, were evaluated. Five independent prognostic factors of death were found: heart rate > 90/min, white blood cells >12,000/mm(3) and respiratory rate >20/min (at early disease stage), coagulopathy and gastrointestinal bleeding (at maximal disease stage). In addition, systemic inflammatory response syndrome (SIRS) occurred at a much higher percentage among non-survivors throughout hospitalization. We found tachycardia, leukocytosis, tachypnea, coagulopathy, gastrointestinal bleeding and SIRS were associated with a poor outcome in DRESS patients. DRESS patients with persistent SIRS during hospitalization were also associated with a higher mortality risk. Early recognition and prompt intervention in these factors may improve outcome.