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To assess the feasibility, safety, and impact on relative hypoglycemia of liberal versus conventional blood glucose concentration targets in critically ill diabetic patients.Prospective, open-label, sequential-period exploratory study.A 22-bed multidisciplinary ICU of a tertiary care hospital in Australia.Eighty adult diabetic patients, 40 from the conventional before period and 40 from the liberal after period.Blood glucose concentration targets were 6–10 mmol/L during the before period and 10–14 mmol/L during the after period.We used admission glycated hemoglobin to estimate premorbid baseline blood glucose concentration. We defined glycemic distance as the difference between blood glucose concentration in ICU and baseline blood glucose concentration. During the first 48 ICU hours, we recorded absolute (blood glucose concentration, < 3.9 mmol/L) and relative (glycemic distance, > 30% below baseline) hypoglycemia rates, insulin administration, and outcomes. The groups had similar baseline characteristics. We observed a negative glycemic distance in 248 of 488 blood glucose concentrations (50.8%) during the before period and 164 of 485 (33.8%) during the after period (p < 0.001). We detected relative hypoglycemia in 20 (50.0%) and nine (22.5%) patients in the before and after periods, respectively (p = 0.01). On day 1, 50.0% and 16.7% received insulin in the before and after periods (p = 0.007). ICU and hospital length of stay and mortality were similar between groups.In a safety cohort of critically ill diabetic patients, a blood glucose concentration target of 10–14 mmol/L resulted in fewer episodes of negative glycemic distance or relative hypoglycemia and reduced insulin administration compared with a target of 6–10 mmol/L.