Objective: The aim of this study was to evaluate the safety and efficacy of a new intravenous (IV) regular human insulin infusion (RHI) algorithm for glycemic control in critically ill patients with renal failure. Methods: Adult trauma patients with renal failure who received a new RHI algorithm were compared with those who received the discontinued RHI algorithm (historical control). Target blood glucose (BG) concentration was 70 to 149 mg/dL (3.9-8.3 nmol/L). Patients were evaluated for 7 d while receiving the RHI infusion and continuous enteral or parenteral nutrition. Results: Mean BC was higher for the new RHI algorithm group (n = 25) compared with control (n = 21): 145 +/- 10 mg/dL or 8.1 +/- 0.6 mmol/L versus 133 +/- 14 mg/dL or 7.4 +/- 0.8 mmol/L (P = 0.001). The new RHI algorithm resulted in less time within the target BC range (11.9 +/- 2.5 h/d versus 16.1 +/- 3.3 h/d; P = 0.001); however, BGs were within 70 to 179 mg/dL (or 3.9-10 mmol/L) for 16.3 +/- 2.6 h/d. The proportion of patients who experienced an episode of moderate hypoglycemia (BC 40-60 mg/dL or 2.2-3.3 mmol/L) or severe hypoglycemia (BC <40 mg/dL or 2.2 mmol/L) was decreased (32% versus 76%; P = 0.001) and eliminated (0% versus 29%, P = 0.006), respectively. Conclusions: The new RHI algorithm improved patient safety by decreasing the prevalence of moderate hypoglycemia and eliminating severe hypoglycemia. The duration of glycemic control within the target BC range was decreased, but acceptable within a higher target BC ceiling. (C) 2014 Elsevier Inc. All rights reserved.