Background About one-third of patients with acute ischemic stroke will endure early neurological deterioration (END), which leads to increased mortality and functional disability. A better understanding of risk factors for END is still required. Objective The aim of this study was to determine the risk factors of END in ischemic stroke patients. Patients and methods One hundred and twenty patients with first ever ischemic stroke were included in this study. All patients were clinically evaluated to determine the risk factors. END was assessed using the National Institute of Health Stroke Scale (NIHSS) after acute ischemic stroke. Laboratory and radiological investigations were done for all patients. Results In all, 35% patients showed clinical END after stroke onset and 65% patients were stable or improved. END patients had statistically significant high body temperature, increased leukocyte count, serum blood glucose, triglycerides, NIHSS at admission, high-sensitivity C-reactive protein, and infarction size. Multivariable logistic regression analysis for different variables showed that leukocyte count, stroke severity using NIHSS, and lesion size were independent factors associated with neurological deterioration. Conclusion Stroke severity, white blood cell, and lesion size of infarction were the only independent factors associated with END