BACKGROUND Dengue fever has seen a significant re-emergence in Southeast Asia. Associated with the rise of dengue has been the increase in dengue-associated mortality. To better understand the predictors of mortality, we conducted a review of hospitalized adult dengue infections within our institution. METHODS This was a retrospective case-control study of dengue-associated deaths at a large tertiary care hospital. RESULTS In 2004, of 3186 cases of dengue fever (DF)/hemorrhagic dengue fever (DHF) admitted to our institution, there were 130 cases of DHF and seven dengue-associated deaths (case-fatality rate 5.4%). At least three of the seven fatal cases had serological evidence of primary dengue infection. All dengue-mortality cases had rapidly progressive clinical deterioration at an average of day 4 of fever with intensive care admission occurring on a mean of 5.6 days of fever. Adult respiratory distress syndrome, disseminated intravascular coagulopathy, and multi-organ failure were the most common causes of death despite early hospitalization, intravenous fluid, and blood-product support. CONCLUSIONS Dengue is associated with severe disease, and deaths do occur despite current supportive management. Fatal DHF/dengue shock syndrome (DSS) does occur in adults and in primary dengue infection. Better early predictors of disease severity and clinical interventions are needed.