OBJECTIVES: Fear of hypoglycemia influences Health-Related Quality of Life (HRQoL) in type 2 diabetes mellitus (T2DM) patients implying changes in clinical management. The aim of the study is to explore the way that fear for hypoglycemia modifies HRQoL in T2DM patients in Spain. METHODS: Observational, cross-sectional, multicentre design. T2DM patients diagnosed from at least 1 year were recruited consecutively. Use of research tools: 1) Audit of Diabetes-Dependent Quality of Life/ADDQoL questionnaire [-9 to +9, more negative scores indicate greater negative impact of diabetes on QoL]; 2) Worry Subscale of the Hypoglycaemic Fear Survey-II (HFS-II) [0-72, higher scores indicate increased fear]; 3) Visual Analogue Scales (VAS) measuring fear and impact of hypoglycemia [0-10, higher scores indicate greater fear and impact of hypoglycemia]. RESULTS: A total of 3,812 patients (661 health care centers; 17 regions) participated in the study [men (53.57%); mean(SD) age 63.70(11.37) years; retired (43.02%); mean(SD) time from T2DM diagnosis 9.67(6.91) years. 44.88% referred at least one episode of hypoglycemia in the previous six months, more frequent (40.50%) and severe (43.37%) in the morning. Mean (SD) HFS-II subscale score was higher in patients who reported hypoglycemic episodes during the previous six months [31.32(15.71)] compared to those who did not [18.85(16.03)](p<0.0001). Mean (SD) ADDQoL scores showed a greater significant negative impact of T2DM on QoL in patients with hypoglycemia [-2.48(1.61)] than in those with no previous episodes [-1.64(1.36)](p<0.0001). They also scored significant higher the influence of fear for hypoglycemia on everyday life [VAS mean (SD) 5.19(2.68)], on daily activities [VAS mean (SD) 5.98(2.59)] and in relation to other health problems [VAS mean (SD) 5.50(2.72)] compared to patients with no previous hypoglycemia episodes [VAS mean (SD) 1.73(2.30); 2.89(2.82) and 2.73(2.72), respectively](p<0.0001). CONCLUSIONS: Fear of hypoglycemia negatively influences T2DM patients HRQoL particularly when episodes of hypoglycemia had taken place during the previous six months.