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To determine whether glycemic derangements are more effectively controlled using software-guided insulin dosing compared with paper-based protocols.We prospectively evaluated consecutive critically ill patients treated in a tertiary hospital surgical intensive care unit (ICU) between January 1 and June 30, 2008, and between January 1 and September 30, 2009. Paper-based protocol insulin dosing was evaluated as a baseline during the first period, followed by software-guided insulin dosing in the second period. We compared glycemic metrics related to hyperglycemia, hypoglycemia, and glycemic variability during the 2 periods.We treated 110 patients by the paper-based protocol and 87 by the software-guided protocol during the before and after periods, respectively. The mean ICU admission blood glucose (BG) level was higher in patients receiving software-guided intensive insulin than for those receiving paper-based intensive insulin (181 vs 156 mg/dL; P=.003, mean of the per-patient mean). Patients treated with software-guided intensive insulin had lower mean BG levels (117 vs 135 mg/dL; P=.0008), sustained greater time in the desired BG target range (95-135 mg/dL; 68% vs 52%; P=.0001), had less frequent hypoglycemia (percentage of time BG level was <70 mg/dL: 0.51% vs 1.44%; P=.04), and showed decreased glycemic variability (BG level per-patient standard deviation from the mean: ±29 vs ±42 mg/dL; P=.01).Surgical ICU patients whose intensive insulin infusions were managed using the software-guided program achieved tighter glycemic control and fewer glycemic derangements than those managed with the paper-based insulin dosing regimen.