Introduction: The World Health Organization (WHO) definition of stroke is: “rapidly developing clinical signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 hours or longer or leading to death, with no apparent cause other than of vascular origin”. The pathological background for stroke may either be Thrombotic or hemorrhagic disturbances of the cerebral blood circulation. Thrombotic cerebral infarction results from the atherosclerotic obstruction of large cervical and cerebral arteries, with ischemia in all or part of the territory of the occluded artery. Hyperhomocysteinemia has been emerging as an independent risk factor for atherosclerosis. Several workers opined that moderately elevated plasma Homocysteine (Hcy) concentration might be an independent risk factor for cerebrovascular disease including stroke and transient ischaemic attack. Material and Methods: The study is a hospital based observational study was conducted in the Department of General Medicine at ACSR Government Medical College, Nellore from Dec 2022 to October 2023. 31 patients with thrombotic stroke(cases) and 31 subjects without thrombotic stroke (controls) and other comorbid conditions that affect serum homocysteine were included in the study. Venous blood samples were collected in tubes containing disodium EDTA. Homocysteine assay is based on the measurement of co-substrate conversion product. Results: In the present study, the mean age ± SD of cases was 55.03±14.51. The mean age of males was 51.68±13.45 and the mean age of females was 60.33±15.11. The mean age in control group was 51.22±13.77. The mean serum homocysteine level in the present study, in cases was 25.98±11.95. The mean homocysteine level in males was 7.83±14.29. The mean in females was 23.05±5.67. The mean homocysteine level in control group was 7.19±3.51. Mean homocysteine level of cerebral ischemic stroke females was 14.86 ± 5.34. The mean homocysteine level in controls was 7.428 ± 4.091. The mean homocysteine level in controls was 12.30± 4.68. The mean cholesterol of the cases was167.67±40.68. The mean LDL in the study was 89.74±27.38. The mean HDL was 38.48±10.92. Conclusions: Serum homocysteine levels were significantly higher in those paients with stroke when compared to those without stroke. Apparently, Serum homocysteine level is an independent risk factor for thrombotic stroke.