The objective of this study was to examine whether setting the low glucose alarm of a Guardian® REAL-Time continuous glucose monitoring system (CGMS) to 80 mg/dl for 3 days and providing instructions to users reduce the risk of hypoglycemia under free-living conditions in individuals with type 1 diabetes mellitus (T1DM). Fourteen participants with T1DM aged 26.1±6.0 years (mean±standard deviation) were fitted with a CGMS and assigned for 3 days to either an alarm [low and high blood glucose (BG) alarms set at 80 and 200 mg/dl, respectively] or no alarm condition, with each treatment administered to all participants following a counterbalanced design. All participants were given detailed instructions on how to respond appropriately to low glucose alarms. The CGMS with alarm reduced the incidence of hypoglycemia (CGMS readings≤65 mg/dl) by 44% as well as the time spent below this hypoglycemic threshold by 64% without increasing average BG levels. However, the CGMS with alarm had no effect on the incidence of symptomatic hypoglycemia. Short-term use of the CGMS with alarm, together with appropriate instructions for users, reduces the incidence and duration of hypoglycemia, but only to a limited extent, in part because it overestimates BG in the low glucose range.