: This study aims to investigate the role of fatty acid ratios, specifically DHA/ARA and EPA/ARA, in predicting severe disability and mortality in stroke patients and compare these ratios with conventional risk factors such as age, sex, hypertension, diabetes, and dyslipidemia. : A prospective study was conducted involving 298 consecutive acute ischemic stroke patients (within 72 h of onset). Fatty acid ratios were measured from plasma, and all patients' evolution was followed through hospitalization. Binary logistic regression analysis was used to identify predictors of severe disability at discharge (Rankin 4-6) and in-hospital mortality, including fatty acid ratios and conventional risk factors. : A higher DHA/ARA ratio was associated with a reduced chance of severe disability (OR = 0.81), while a higher EPA/ARA ratio was associated with an increased chance of severe disability (OR = 1.70). Age was a significant factor, with older age (median 70 years) associated with a lower survivability chance (OR = 0.93) and a higher likelihood of severe disability when surviving. Fatty acid ratios did not significantly affect mortality outcomes. For male patients, EPA/AA ratios showed a powerful association with severe disability ( = 0.045), while no significant effect of fatty acids was observed in females. : Fatty acids were significant predictors of severe disability in patients with acute ischemic stroke, independent of conventional risk factors, but without having any effect on in-hospital mortality. Age remained the only significant conventional risk factor predictor of outcome. Integrating fatty acid ratios alongside conventional risk factors may improve predictions of severe post-stroke disability, potentially guiding more personalized interventions for stroke patients.