Intensive insulin therapy has widely and rapidly been adopted as the standard of care for the treatment of hyperglycemia in the intensive care unit (ICU). Variability in blood glucose is increasingly recognized as an important factor in outcomes in the chronic diabetic in addition to hemoglobin A1C. We tested the hypothesis that measures of blood glucose variability would be associated with mortality in the surgical ICU. A retrospective analysis of a cohort of ventilated, critically ill surgical and trauma ICU patients placed on an automated insulin protocol was performed. Blood glucose (BG) variability was measured by comparing standard deviation, percentile values, successive changes in blood glucose, and by calculating the triangular index for various glucose-related indices. Eight hundred and fifty-eight patients had 46,474 blood glucose and insulin dose data points. One hundred and twenty-one patients died for an overall mortality rate of 14 per cent. Several measures of blood glucose variability (maximum successive change in BG and the triangular index) were different between the groups despite similar mean BG between survivors (117 mg/dL) and nonsurvivors (118 mg/dL). Increased blood glucose variability is associated with mortality in the surgical ICU. Further studies should focus on the demographic, clinical, and genetic factors responsible for this observation and identify strategies to minimize BG variability.