To better understand risk factors for the development of diabetic hyperosmolar state (DHS), we studied 135 patients with DHS and 135 age-matched randomly selected diabetic controls admitted to two general hospitals during an 11-year period. To be eligible for the study, patients had to have a hospital admission glucose level of greater than 600 mg/dL (33.3 mmol/L) and an osmolality of greater than 325 mOsm/L (32.5 mmol/L). Patients were significantly more likely than controls to be female (71% vs 53%), to be nursing-home residents (28% vs 15%), to be newly diagnosed diabetics (36% vs 7%), to have a history of dementia (18% vs 8%), and to have an acute infection at the time of admission to the hospital (39% vs 19%). Multivariate analysis revealed three significant independent predictors of DHS: female gender, newly diagnosed diabetes, and acute infection; nursing-home residence and dementia had no independent effect. Other functionally debilitating diseases, acute illnesses, or medications that may impair glucose tolerance were not significantly associated with DHS.