BACKGROUND: Accuracy and frequency of glucose measurement is essential to achieve safe and efficacious glucose control in the intensive care unit. Emerging continuous glucose monitors provide frequent measurements, trending information, and alarms. The objective of this study was to establish the level of accuracy of continuous glucose monitoring (CGM) associated with safe and efficacious glucose control in the intensive care unit. METHODS: We evaluated 3 established glucose control protocols [Yale, University of Washington, and Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR)] by use of computer simulations. Insulin delivery was informed by intermittent blood glucose (BG) measurements or CGM levels with an increasing level of measurement error. Measures of glucose control included mean glucose, glucose variability, proportion of time glucose was in target range, and hypoglycemia episodes. RESULTS: Apart from the Washington protocol, CGM with mean absolute relative deviation (MARD) ≤ 15% resulted in similar mean glucose as with the use of intermittent BG measurements. Glucose variability was also similar between CGM and BG-informed protocols. Frequency and duration of hypoglycemia were not worse by use of CGM with MARD ≤ 10%. Measures of glucose control varied more between protocols than at different levels of the CGM error. CONCLUSIONS: The efficacy of CGM-informed and BG-informed commonly used glucose protocols is similar, but the risk of hypoglycemia may be reduced by use of CGM with MARD ≤ 10%. Protocol choice has greater influence on glucose control measures than the glucose measurement method.