OBJECTIVE: To establish the prevalence of self-reported hypoglycemia among ambulatory patients with diabetes and assess its impact on health-related quality of life (HRQoL). METHODS: This study was a cross-sectional analysis of a postal survey disbursed during the first quarter of 2010 to 875 adults with type 1 or 2 diabetes identified on the basis of an index clinical encounter for diabetes management between August 1, 2005 and June 30, 2006. The survey included questions regarding hypoglycemia, self-rating of health, and questions adapted from Confidence in Diabetes Self-Care, Generalized Anxiety Disorder-7, EuroQol5-D, and the Hypoglycemic Fear Survey. Data were analyzed using a two-sample t test for continuous variables and a chi-square test for categorical variables, with multivariate analysis to adjust for age, gender, diabetes duration, and Charlson comorbidity index. RESULTS: The survey was completed by 418 patients (47.8% response rate). Of the respondents, 26 of 92 (28.3%) with type 1 and 55 of 326 (16.9%) with type 2 diabetes reported at least one episode of severe hypoglycemia within the previous 6 months. Fear of hypoglycemia, including engagement in anticipatory avoidance behaviors, was highest in patients with type 2 diabetes reporting severe hypoglycemia and all patients with type 1 diabetes (P<.001). HRQoL was lower in patients with type 2 (but not type 1) diabetes reporting severe hypoglycemia (P<.01). CONCLUSION: Clinicians and health systems should incorporate screening for hypoglycemia into the routine health assessment of all patients with diabetes. Fear of hypoglycemia places patients at risk for counterproductive behaviors, impairs HRQoL, and should be considered in individualizing glycemic goals.