Copeptin is a stable by-product of arginine-vasopressin synthesis and reflects its secretion. The objective of the study was to evaluate the predictive value of copeptine on functional outcome at 90-day follow-up from stroke onset. We conducted a prospective, observational cohort study in the emergency department of two hospitals and enrolled 125 patients with acute ischemic stroke. Plasma copeptin concentrations, determined by a CT-proAVP-luminescence-immunoassay, were measured. There was a good correlation between levels of plasma copeptin and NIHSS score (r = 0.733, P < 0.01). In the 41 patients (32.8 %) with a poor functional outcome, copeptin levels were higher compared with those in patients with a favorable outcome (27.3; IQR, 14.9-34.8 pmol/L vs. 12.9; IQR, 9.4-21.6 pmol/L; P < 0.0001). Copeptin levels in 18 patients who died were more than two times greater as compared to patients who survived (32.4; IQR, 18.7-38.5 pmol/L vs. 15.1; IQR, 12.4-24.6 pmol/L; P < 0.0001). After adjusting for all other significant outcome predictors, copeptin level remained an independent predictor for poor functional outcome and mortality with an odds ratio of 3.12 (95 % CI 1.54-6.46), 3.16 (95 % CI 0.92-6.15), respectively. Our study suggests that copeptin levels are a useful tool to predict outcome and mortality 3 months after acute ischemic stroke and have a potential to assist clinicians.