OBJECTIVE To determine the incidence and manifestations of hypoglycemia in hospitalized patients receiving antihyperglycemic therapy. METHODS The study was a 3-month prospective review of consecutive medical records of all adult, nonpregnant hospitalized patients at a 675-bed university hospital who experienced at least 1 blood glucose (BG) <or= 60 mg/dL within 48 hours of receiving an antihyperglycemic agent. RESULTS Of 2174 patients receiving antihyperglycemic agents, 206 (9.5%) experienced 484 hypoglycemic episodes. Of these episodes, 29% occurred in patients with type 1 diabetes, 23% in the ICU, and 72% in patients receiving only insulin for hyperglycemia. More than 1 episode was experienced by 44% of the 206 patients. Furthermore, 4% (20 of 484) of the hypoglycemic episodes were associated with a hypoglycemia-related adverse event, defined as symptoms, signs, or injury. The mean BG of these episodes was 43.0 mg/dL, significantly lower than the mean BG of 50.9 mg/dL for the 464 episodes without adverse events (P = .01). One-third of the adverse events occurred with a BG between 50 and 60 mg/dL; half the adverse events, 10 episodes or 2% of all hypoglycemic episodes, were serious, involving seizures or an unresponsive patient. A decrease in enteral intake accounted for 40% of the episodes; none was attributed to medication error. Less than half the hypoglycemic patients had documented euglycemia within 2 hours. Sulfonylurea agents were associated with higher rates of hypoglycemia than were other oral agents. CONCLUSIONS Hypoglycemia in hospitalized patients taking antihyperglycemic agents is common; 1 in 25 episodes is associated with an adverse event. Opportunities exist to improve care, particularly around discontinuation of feeding.