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Abstract Aim Perioperative tight blood glucose (BG) control using insulin therapy after major surgery is a difficult, time-consuming task that also raises some concerns over the risk of severe hypoglycaemia. The aim of the present prospective study was to evaluate the efficacy and safety of an insulin therapy protocol in use at our institution. Methods A total of 230 consecutive patients (mean ± SD age: 67 ± 11 years; diabetic patients: n = 62) undergoing cardiac surgery (coronary artery bypass grafting: n = 137; 20% off-pump) or intrathoracic aortic ( n = 10) surgery were included. BG control was managed according to an insulin therapy protocol, described by Goldberg et al. (2004) [11] , in use for 6 months in our intensive care unit. Insulin infusion rate and frequency of BG monitoring were both adjusted according to: (1) the current BG value; (2) the previous BG value; and (3) the current insulin infusion rate. Efficacy was assessed by the percentage of time spent at the target BG level (100–139 mg/dL) intraoperatively and during the first 2 postoperative days (POD). Results All patients received postoperative insulin therapy. Patients spent 57.3% and 69.7% of time within the BG target range on POD 1 and 2, respectively. The percentage of time was significantly higher in nondiabetics than in diabetics. Mean BG measurements per patient intraoperatively, on POD 1 and on POD 2 were 4 ± 1, 10 ± 2 and 7 ± 2, respectively. No patient experienced any severe hypoglycaemic events (BG < 50 mg/dL). Conclusion This study showed that a BG target of 100–139 mg/dL can be safely achieved with an insulin therapy protocol that can be routinely used in everyday clinical practice.