Background: Stress-induced hyperglycemia is a common metabolic disorder in Intensive Care Unit (ICU) cases (30-60%) in diabetic and non-diabetic patients. It is related to increased rates of mortality and morbidity. Objective: The aim of the current work was to compare between glycemic control in single dose long-acting subcutaneous insulin glargine injection and standard continuous regular insulin infusion in the same critical case. Patients and methods: This prospective clinical study period was 72 hours for every patient and conducted on 111 patients aged 20-70 years with targeted blood glucose (BG) level ranging from 100 to 200 mg/dl using a different calculated dose of standard insulin infusion according to conventional sliding scale for the 1st 24hr of the study before conversion into insulin glargine single dose injection with 1-hour washout transition period. Results: APACHE II score was significantly higher in "Uncontrolled hyperglycemia" group in comparison to "Uncontrolled hypoglycemia" group (P=0.030) but insignificantly different between "Controlled" group and "Uncontrolled hyperglycemia" group and between "Controlled" group and "Uncontrolled hypoglycemia" group. Daily units of insulin and mean BG level at 1st day were significantly lower in "Uncontrolled hypoglycemia" group in comparison to "Controlled" group (P=0.002 and 0.002 respectively) and "Uncontrolled hyperglycemia" group (P=0.004 and 0.006 respectively) but insignificantly different between "Controlled" group and "Uncontrolled hyperglycemia" group. While mean BG level was insignificantly different among the three groups at 2nd day, it was insignificantly different between "Controlled" group and "Uncontrolled hyperglycemia" group at 3rd day. Conclusion: It could be concluded that the use of 100% conversion single dose of long-acting insulin glargine for control of hyperglycemia in critical ICU patients can be considered as an accepted good alternative to the classic use of continuous regular insulin infusion.