Background and Purpose Micro ribonucleic acid-150-5p (miR-150-5p) regulates proinflammatory cytokines as well as vessel integrity. We evaluated the incremental prognostic value of logarithm (log) of miR-150-5p plasma levels after ischemic stroke. Methods In a prospective cohort study, levels of miR-150-5p were measured within 72 hours of symptom onset in 329 ischemic stroke patients. The outcome measures were unfavorable functional outcome (assessed by the modified Rankin Scale score >2) and mortality within 90 days. Logistic regression and Cox proportional hazards models were fitted to estimate odds ratio (OR), respectively hazard ratio (HR) and 95% confidence interval (CI) for the association between log-miR-150-5p and the outcome measures. The discriminatory accuracy was assessed with the area under the receiver-operating-characteristic curve (AUC) and the incremental prognostic value was estimated with the net reclassification index. Results After adjusting for demographic and vascular risk factors, lower log-miR-150-5p levels were independently associated with mortality (HR 0.21 [95% CI, 0.08–0.51], P=0.001) but not functional outcome (OR 1.10 [95% CI, 0.54–2.25], P=0.79). Adding log-miR-150-5p improved the discriminatory accuracy of the best multivariate model to predict mortality from an AUC of 0.91 (95% CI, 0.88–0.95) to 0.92 (95% CI, 0.88–0.96 Likelihood-ratio test-P<0.001), and resulted in a net reclassification index of 37.3% (95% CI, 0.28–0.52). Conclusions In patients with ischemic stroke, log-miR-150-5p is a novel prognostic biomarker, highly associated with mortality within 90 days, improving risk classification beyond traditional risk factors.