OBJECTIVE: To estimate the impact of hypoglycemia on the Quality of Life (QoL) and its prevalence in patients with type 2 diabetes mellitus (T2DM) in Greece. DESIGN: A cross-sectional epidemiological study was conducted in 6631 patients with T2DM. QoL was assessed with the patient self-administered ADDQoL-19. Reliability analysis of patients’ outcomes was performed to assess internal consistency of the ADDQoL-19. Patients were categorized according to hypoglycemia experience and diabetes control. Controlled patients were considered as having Hb1Ac <7% (53mmol/mol) and hypoglycemic episodes were defined as laboratory-confirmed clinical symptomatic events. RESULTS: In total, 59% of the sample had HbA1c >7% (53mmol/mol) and 20.4% of patients had a history of laboratory-confirmed hypoglycemia. The mean age was 60 years and the mean T2DM duration was 10 years. The mean QoL score was −3.09±1.9 for the total sample and the mean score of non-hypoglycemic patients was −3.05±2, while the respective score of hypoglycemic patients was −3.26 ±1.8, (p≤0.001). Similar results were observed in the group of controlled and uncontrolled patients, who scored −2.73±1.7 and −3.33±1.9, respectively (p≤0.001). Comparable results were identified in the majority of the ADDQoL-19 instrument dimensions. CONCLUSIONS: The QoL of T2DM patients is affected significantly by hypoglycemia and the level of disease control. In diabetes treatment, the ultimate goal should be optimal glycemic control without debilitating hypoglycemic episodes which compromise patients’ QoL.