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Background This study investigated the optimal coefficient of variance (%CV) for preventing hypoglycemia based on real-time continuous glucose monitoring (rt-CGM) data in people with type 1 diabetes mellitus (T1DM) already achieving their mean glucose (MG) target. Methods Data from 172 subjects who underwent rt-CGM for at least 90 days and for whom 439 90-day glycemic profiles were available were analyzed. Receiver operator characteristic analysis was conducted to determine the cut-off value of %CV to achieve time below range (%TBR)< 54mg/dL <1 and =0. Results Overall mean glycosylated hemoglobin was 6.8% and median %TBR< 54mg/dL was 0.2%. MG was significantly higher and %CV significantly lower in profiles achieving %TBR< 54mg/dL <1 compared to %TBR< 54mg/dL ≥1 (all P<0.001). The cut-off value of %CV for achieving %TBR< 54mg/dL <1 was 37.5%, 37.3%, and 31.0%, in the whole population, MG >135 mg/dL, and ≤135 mg/dL, respectively. The cut-off value for %TBR< 54mg/dL=0% was 29.2% in MG ≤135 mg/dL. In profiles with MG ≤135 mg/dL, 94.2% of profiles with a %CV <31 achieved the target of %TBR< 54mg/dL <1, and 97.3% with a %CV <29.2 achieved the target of %TBR<54 mg/ dL=0%. When MG was >135 mg/dL, 99.4% of profiles with a %CV <37.3 achieved %TBR< 54mg/dL <1. Conclusion In well-controlled T1DM with MG ≤135 mg/dL, we suggest a %CV <31% to achieve the %TBR< 54mg/dL <1 target. Furthermore, we suggest a %CV <29.2% to achieve the target of %TBR< 54mg/dL =0 for people at high risk of hypoglycemia.