OBJECTIVE - The Medtronic MiniMed Continuous Glucose Monitoring System (CGMS) is designed to continuously monitor interstitial fluid glucose levels within a range of 40-400 mg/dl. It is considered an important tool for overnight glucose monitoring. The goal of this study was to determine the accuracy of this system in individuals with tightly controlled diabetes. RESEARCH DESIGN AND METHODS - Seven adolescents and young adults with HbA1c levels 6.6 ± 0.6% (range 5.7-7.1) were admitted to the Clinical Research Center. Simultaneous glucose measurements obtained by glucose analyzer, Accu-Check Advantage meter, and CGMS were compared. The analyzer levels were considered the standard. RESULTS - The CGMS results were lower than analyzer readings in 74% of simultaneous pairs of tests performed during the 24-h period; the average correlation was 0.76. There was a trend for the poorest correlation to occur in patients with the narrowest range in daily glucose levels. When the lowest CGMS reading of the night was compared with the simultaneous analyzer reading, the CGMS level was lower in all cases by an average of 38 ± 15%. In six of seven patients, the discrepancy was believed to be clinically significant; in at least four patients, overnight glucose levels reported by CGMS were falsely low, in a range that might have resulted in inappropriate reduction of overnight insulin dose. CONCLUSIONS - CGMS reports of asymptomatic nighttime hypoglycemia may be spurious and should be interpreted with caution in patients with tightly controlled diabetes.