Background The optimal target range for blood glucose in critically ill patients remains unclear. Methods Within 24 hours after admission to an intensive care unit(ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter(4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter(10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. Results Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients(27.5%) in the intensive-control group and 751(24.9%) in the conventional-control group died(odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative(surgical) patients and nonoperative(medical) patients(odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P = 0.10). Severe hypoglycemia(blood glucose level, <40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients(6.8%) in the intensive-control group and 15 of 3014(0.5%) in the conventional-control group(P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU(P = 0.84) or hospital(P = 0.86) or the median number of days of mechanical ventilation(P = 0.56) or renal-replacement therapy(P=0.39). Conclusions In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter.(ClinicalTrials.gov number, NCT00220987.) Copyright © 2009 Massachusetts Medical Society.