BACKGROUND: Hypoglycemia is the most common complication in insulin treated diabetes. Though mostly mild, it can be fatal in rare cases: It is hypothesized that hypoglycemia related QTc prolongation contributes to cardiac arrhythmia. OBJECTIVE: To evaluate influence of nocturnal hypoglycemia on QTc and heart rate variability (HRV) in children with T1D. METHODS: Children and adolescents with T1D for at least 6 months participated in an observational study using continuous glucose monitoring (CGM) and Holter electrocardiogram for five consecutive nights. Mean QTc was calculated for episodes of nocturnal hypoglycemia (<3.7 mmol/L) and compared to periods of the same duration preceding hypoglycemia. HRV (RMSSD, low and high frequency power LF and HF) was analyzed for different 15 min intervals: before hypoglycemia, onset of hypoglycemia, before/after nadir, end of hypoglycemia and after hypoglycemia. RESULTS: Mean QTc during hypoglycemia was significantly longer compared to euglycemia (412 +/- 15 vs. 405 +/- 18 ms, p = 0.005). HRV changed significantly: RMSSD (from 88 +/- 57 to 73 +/- 43 ms) and HF (from 54 +/- 17 to 47 +/- 17nu) decreased from before hypoglycemia to after nadir, while heart rate (from 69 +/- 9 to 72 +/- 12 bpm) and LF (from 44 +/- 17 to 52 +/- 21 nu) increased (p = 0.04). CONCLUSION: A QTc lengthening effect of nocturnal hypoglycemia in children with T1D was documented. HRV changes occurred even before detection of nocturnal hypoglycemia by CGM, which may be useful for hypoglycemia prediction.