Introduction: Worldwide, in adults stroke is a 2 nd most common & leading cause of disability and death. The incidence rises steeply with age and in many developing countries because of adoption of less healthy lifestyles. Apart from hypertension, smoking, hyperlipidemia and diabetes mellitus, Stress Hyperglycemia (Hyperglycemia occurred during acute ischemic stroke in a non diabetic patient) is thought one of the vulnerable factor that affects the acute phase of stroke and 30 days mortality and out-come. Stress hyperglycemia (SH) i.e.; Random Blood Sugar level >121 mg/dl or > 6.1 mmol/ L has been found in 2/3 rd of all stroke patients and in almost 1/2 of the acute Ischemic Stroke (IS) population. A prospective, multiple meta-analyses & case control studies have reported more than 3- fold increase in 30-days mortality in non diabetic (stress) hyperglycemia compared with a 2-fold increase in known diabetics. Imaging studies suggest that metabolic derangements contribute to detrimental effects on short term mortality, infarct size & clinical outcome. Various factors have been proposed, those become activated during cascade of SH with IS leading; Vasoconstriction, Prothrombosis & Proinflammation, activation of Hexosamine/ Nitric oxide, Pentose phosphate & Protein Kinase-C pathways respectively. Study Design & Place: This observational and prospective study was conducted from 1 st January 2009 31 st December 2009, at Medical Unit-II in Liaquat University Hospital (LUH) Jamshoro/Hyderabad. Results: Sixty cases were inducted for study, out of these 30 were suffering from IS with SH and 30 were belonging to IS without SH. From these, 38 (63.3%) were male & that of 22 (36.7%) were female. Initially all IS patients with SH, for 01 week were treated by ICU management with Regular Insulin along with other standard stroke-protocol & later with General management for 02-03 weeks. During hospitalization the mortality rate was high in SH patients 10 (33.3%) i.e.; Male were 07 (23.3% & Female were 03 (10%), as compared to patients without SH 02 (06.7%) i.e.; all were Male. While in case of SH the survivors have delayed recovery and poor prognosis but patients without SH have rapid recovery and good prognosis respectively. Conclusion: In our study we found that Stress Hyperglycemia in acute Ischemic Stroke patients increases the duration of hospitalization stay & short term mortality and long term morbidity, therefore, understanding all pathways and developing specific therapies along with critical care of IS patients with SH, may reduce the mortality & morbidity, hence improve outcome & prognosis world wide.