OBJECTIVE: The Diabetes Control and Complications Trial identified an inverse relationship between HbA1c and severe hypoglycemia. We investigated the relationship between hypoglycemia and HbA1c in a large type 1 diabetes cohort on multiple daily injection or insulin pump therapy using blinded continuous glucose monitoring (CGM) data. The impact of real-time CGM on these relationships and how these relationships differ with biochemical definitions of hypoglycemia have also been assessed. RESEARCH DESIGN AND METHODS: CGM data were obtained from the JDRF CGM randomized control trial. Baseline blinded-CGM data were used to assess time in hypoglycemia in all individuals. End-point data from the CGM intervention group were used to assess the impact of CGM. Percentage times <3.9, 3.3, 3.0, and 2.8 mmol/L were calculated and quadratic regression plots drawn. Relationships were analyzed visually, and ANOVA was used to assess relationships between glycemia and time below threshold. RESULTS: J-shaped relationships were observed for all biochemical hypoglycemia thresholds, with the lowest hypoglycemia risk occurring at HbA1c values between 8.1 and 8.6% (65-70 mmol/mol). The use of an average of 5 days/week of CGM flattened the relationships for 3.3, 3.0, and 2.8 mmol/L, and ANOVA confirmed the loss of relationship for the 3.3 mmol/L threshold using CGM. CONCLUSIONS: The relationship between hypoglycemia and HbA1c in a population with type 1 diabetes is J-shaped. Lower HbA1c values are still associated with increased hypoglycemia risk, although the magnitude of risk depends on biochemical threshold. Real-time CGM may reduce the percentage time spent in hypoglycemia, changing the relationship between HbA1c and hypoglycemia.