ABSTRACT: Stress-induced hyperglycemia has been associated with poor outcomes and death in critically ill patients. Blood glucose (BG) variability, a component of stress-related hyperglycemia has recently been reported as a significant independent predictor of intensive care unit and hospital mortality. We sought to evaluate three cases in which intensive insulin therapy was administered using a standardized insulin dosing protocol to normalize the BG and reduce glycemic variability. Point-of-care BG values and other clinical measures were obtained from the medical record of three patients who received intensive insulin therapy. This was a convenience sample of three patients where the BG level had stabilized on a consistent intravenous insulin dose rate for up to 20 hours in a surgical trauma intensive care unit. Data were collected manually and electronically using the Remote Automated Laboratory System-Tight Glycemic Control Module (RALS-TGCM®) BG management and monitoring system. Each case presentation describes a critically ill, nondiabetic patient, requiring continuous intravenous insulin therapy for hyperglycemia. In each instance, BG variability was present in a worsening patient condition after a period of normalization of hyperglycemia with intensive insulin therapy. Although decreasing BG variability is an important aspect of hyperglycemia management, new onset events of variability may be a sentinel warning or occur as a physiologic response to a worsening patient condition. If so, these events warrant rapid investigation and treatment of the underlying problem.