OBJECTIVE: In this study, we evaluated the safety and efficacy of 7-day transcutaneous, real-time, continuous glucose monitoring (CGM) in subjects with insulin-requiring diabetes. RESEARCH DESIGN AND METHODS: Eighty-six subjects were enrolled at five U.S. centers. Subjects wore a sensor inserted under the skin of the abdomen for 7 days during each of three consecutive periods. Data were blinded during period 1 and unblinded during periods 2 and 3. RESULTS: Of the 6,811 matched self-monitoring of blood glucose to sensor values prospectively analyzed, 97.2% fell in the Clarke error grid zones A and B, and median absolute relative difference was 11.4%. After unblinding, subjects reduced time spent at <55 mg/dl by 0.3 h/day, reduced time spent at >240 mg/dl by 1.5 h/day, and increased time in the target zone (81-140 mg/dl) by 1.4 h/day (P < 0.05 for all three comparisons). Improvements were seen in both types 1 and 2 diabetes and with use of both multiple daily injections and continuous subcutaneous insulin infusion. Modal day graphs were generated in six groups of subjects based on HbA1c (A1C) (<or=6, 6-7, 7-8, 8-9, 9-10, and >10%). Mean glucose levels from midnight to 7:00 a.m. (fasting and dawn phenomenon periods) were only normal for subjects with A1C <or=6%. All other groups were hyperglycemic during this and all periods. Reductions in overall mean glucose were achieved for the four highest A1C groupings with unblinded device use. CONCLUSIONS: This is the first report of a real-time, transcutaneous glucose sensor that functioned for 7 days. The use of CGM in the unblinded phase resulted in improvements in target-range glycemia across all A1C values.