Background: Globally, acute ischaemic stroke (AIS) is a leading cause of death and chronic disability. Lipid metabolism and inflammation are crucial to the development and progression of AIS. A new inflammatory biomarker that reflects the equilibrium between pro-inflammatory monocytes and the beneficial anti-inflammatory effects of HDL cholesterol is the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio (MHR). The purpose of this study was to assess the importance of MHR in predicting in-hospital outcomes and stroke severity in patients with AIS.Methods: A prospective observational study was conducted in the Department of General Medicine, K.R. Hospital, Mysore Medical College and Research Institute, Mysuru, from April 2024 to September 2025. Sixty-three patients aged 18–80 years with clinically and radiologically confirmed acute ischemic stroke were included. Clinical details, risk factors, laboratory investigations, and neuroimaging findings were recorded. MHR was calculated using admission monocyte count and HDL cholesterol levels. The National Institutes of Health Stroke Scale (NIHSS) was used to measure the severity of the stroke, and complications, length of hospital stay, and clinical outcomes were used to evaluate in-hospital outcomes. SPSS was used for statistical analysis, and p <0.05 was deemed significant. Results: The majority of patients were aged 40–50 years (34.9%), with a slight male predominance (53.9%). Diabetes mellitus (61.9%) and hypertension (46.0%) were common comorbidities. Higher MHR values were significantly associated with aspiration pneumonia and sepsis (p<0.0001). Patients with mortality and residual neurological deficits demonstrated significantly higher MHR values compared to those who improved clinically (p<0.0001). MHR showed a strong positive correlation with hospital stay duration (r=0.820, p<0.0001) and NIHSS score on day 7 (r=0.717, p<0.0001), indicating greater neurological severity and poorer prognosis.ConclusionMHR is a simple, inexpensive, and readily available biomarker that correlates significantly with stroke severity, in-hospital complications, prolonged hospitalization, and adverse clinical outcomes in acute ischemic stroke. Incorporation of MHR into routine clinical assessment may facilitate early risk stratification and improve patient management.