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Tight glycemic control using intermittent blood glucose measurements is associated with a risk of hypoglycemia. Glucose concentrations can now be measured near continuously (every 5–15 min). We assessed the quality and safety of glycemic control guided by a near-continuous glucose monitoring system in ICU patients.Prospective, cluster-randomized, crossover study.Thirty-five–bed medico-surgical department of intensive care with four separate ICUs.Adult patients admitted to the department and expected to stay for at least 3 days were considered for inclusion if they had persistent hyperglycemia (blood glucose > 150 mg/dL) up to 6 hours after admission and/or were receiving insulin therapy.A peripheral venous catheter was inserted in all patients and connected to a continuous glucose monitoring sensor (GlucoClear; Edwards Lifesciences, Irvine, CA). The four ICUs were randomized in pairs in a crossover design to glycemic control using unblinded or blinded continuous glucose monitoring monitors. The insulin infusion rate was adjusted to keep blood glucose between 90 and 150 mg/dL using the blood glucose values displayed on the continuous glucose monitor (continuous glucose monitoring group—unblinded units) or according to intermittent blood glucose readings (intermittent glucose monitoring group—blinded units).The quality and safety of glycemic control were assessed using the proportion of time in range, the frequency of blood glucose less than 70 mg/dL, and the time spent with blood glucose less than 70 mg/dL (TB70), using blood glucose values measured by the continuous glucose monitoring device. Seventy-seven patients were enrolled: 39 in the continuous glucose monitoring group and 38 in the intermittent glucose monitoring group. A total of 43,107 blood glucose values were recorded. The time in range was similar in the two groups. The incidence of hypoglycemia (8/39 [20.5%] vs 15/38 [39.5%]) and the TB70 (0.4% ± 0.9% vs 1.6% ± 3.4%; p < 0.05) was lower in the continuous glucose monitoring than in the intermittent glucose monitoring group.Use of a continuous glucose monitoring–based strategy decreased the incidence and severity of hypoglycemia, thus improving the safety of glycemic control.