OBJECTIVE: Changes in heart rate variability (HRV) occur at the initiation of hypoglycemia due to sympathetic nervous system activity. We investigated the use of HRV detection by a wearable device as an early alert for hypoglycemia. RESEARCH DESIGN AND METHODS: This proof-of-principle study included 23 patients with type 1 diabetes (14 women, mean age 42 +/- 11 years). Patients wore a VitalConnect HealthPatch for 5 days. Hypoglycemia was defined as glucose </=70 mg/dL (</=3.9 mmol/L) by fingerstick measurement. HRV was analyzed in standardized periods before the hypoglycemic event. RESULTS: Sixty-six hypoglycemic events were recorded. Hypoglycemia caused a typical HRV pattern in 36 (55%) of the hypoglycemic events. Eighteen events (27%) showed an atypical pattern. Ten events were unclassified (15%), and two did not display a change in HRV (3%). CONCLUSIONS: Hypoglycemia causes early changes in HRV that can be detected by a wearable device. Measuring real-time HRV seems promising for early hypoglycemia detection.