OBJECTIVE: To perform an analysis of healthcare resource utilization with intensive insulin therapy, which has recently been shown to reduce morbidity and mortality rates of mechanically ventilated critically ill patients in a surgical intensive care unit. Design: A post hoc cost analysis. SETTING: Surgical intensive care unit. PATIENTS: Patients were 1548 mechanically ventilated patients admitted to a surgical intensive care unit. INTERVENTIONS: A post hoc cost analysis was conducted based on data collected prospectively as part of a large randomized controlled trial. The analysis performed was a healthcare resource utilization analysis in which the cost of hospitalization in the intensive care unit was determined based on length of stay and the frequency of crucial cost-generating morbid events occurring in the intensive and conventional insulin treatment groups. Sensitivity analyses were performed to evaluate the robustness of the findings. Discounting of costs was not performed as treatment was limited to the intensive care stay and follow-up was not continued beyond hospitalization. MEASUREMENTS AND MAIN RESULTS: In the intensive treatment group, total treatment cost was 109,838 Euros (144 Euros per patient). In the conventional treatment group, total treatment cost was 56,359 Euros (72 Euros per patient). The excess cost of intensive insulin therapy was 72 Euros per patient. The total hospitalization cost in the intensive treatment group was 6,067,237 Euros (7931 Euros per patient) compared with 8,275,394 Euros (10,569 Euros per patient) in the conventional treatment group. The excess cost of intensive care unit hospitalization in the conventional vs. intensive treatment group was 2638 Euros per patient. These intensive care unit benefits were not offset by additional costs for care on regular wards. CONCLUSIONS: Intensive insulin therapy, which reduces morbidity and mortality rates of mechanically ventilated patients admitted to a surgical intensive care unit, is associated with substantial cost savings compared with conventional insulin therapy.