OBJECTIVES Hypoglycemia is a side-effect of treatment with oral anti-hyperglycemic agents (OAHAs), especially sulfonylureas (SU). This study assessed the impact of self-reported hypoglycemia on health-related quality of life (HRQoL) among patients with type-2 diabetes mellitus (T2DM), treated with OAHAs. METHODS A cross-sectional, internet-based study was conducted among 2008 participants from the US National Health and Wellness Survey 2007. Patients with self-reported T2DM treated with OAHAs only were included. For each level of self-reported hypoglycemic severity (mild, moderate, severe), frequency (1to 2 episodes, 3 to 6 episodes, or > than once per month) data for six months prior to survey were collected. Very severe hypoglycemia (medical assistance required) was recorded as either one episode or >= to two episodes. Utility was measured using the EQ-5D, and fear of hypoglycemia using the Worry subscale of the Hypoglycemia Fear Survey II (HFS). RESULTS Mean age was 58 (±11) years, 43% were female, and 72.2% reported HbA1c goal attainment (<7%). The proportions of patients on SU monotherapy, SU combination therapy, and other treatment regimens were 10.7%, 39.7%, and 49.6%, respectively. Hypoglycemic episodes were reported by 61.6% of patients (45.6% mild, 37.4% moderate, 13.2% severe and 3.8% very severe). After adjusting for age, gender, weight gain, microvascular and macrovascular complications, the utility scores decreased by increasing severity and frequency of hypoglycemic episodes (with reference = no hypoglycemia), i.e., 0.008, 0.013, 0.015 for mild respectively, 0.046, 0.061, 0.11 for moderate, 0.089, 0.16, 0.27 for severe, and 0.17, 0.27 for very severe, whereas HFS scores increased, 4.6, 5.5, 7.8 for mild, 11.4, 15.2, 13.8 for moderate, 15.5, 20.1, 25.5 for severe, and 25.6, 26.6 for very severe. CONCLUSIONS Self-reported hypoglycemia was experienced by over half of the patients on OAHAs and was associated with reduced quality of life. The magnitude of the reduction increased with frequency and severity of hypoglycemic episodes.