This study evaluated serum levels of novel adipokines in acute ischemic stroke (AIS) and their association with prognosis. We enrolled 168 patients with AIS and 58 stroke-free age- and sex-matched individuals (controls). Clinical parameters, carotid ultrasound, metabolic profile, vaspin, apelin, visfatin, and ghrelin were assayed. Stroke-patients were sampled at hospital admission and were prospectively followed-up (median 16 months) for the cardiovascular endpoint (cardiovascular death/stroke/myocardial infarction). At admission, stroke-patients appeared with higher levels of systolic blood pressure, hsCRP and worse metabolic profile (p < 0.05), (p > 0.05). Compared to controls, AIS group had significantly higher serum concentrations of visfatin (22.92 ± 9.72 ng/ml vs 16.56 ± 7.82 ng/ml, p = 0.006) and lower of vaspin (0.94 ± 0.43 ng/ml vs 1.84 ± 0.82 ng/ml, p = 0.019) and ghrelin (3.47 ± 1.44 ng/ml vs 5.93 ± 2.78 ng/ml, p < 0.001), while apelin did not differ between groups. Similar differences in adipokines were found between stroke subgroups with and without significant ipsilateral carotid stenosis (>50%) (p < 0.05). In stepwise logistic regression analysis adjusted for diabetes, hypertension, dyslipidemia and age, visfatin (p = 0.026) and ghrelin (p = 0.012) proved to be independent predictors of AIS. During follow-up, 27 patients achieved cardiovascular endpoint. In addition to coronary artery disease and NIHSS score, visfatin serum levels was associated with cardiovascular endpoint (HR: 1.255, 95% CI: 1.025–1.576). Our results suggested the association of AIS with higher visfatin and lower vaspin and ghrelin serum levels. Visfatin levels can be a predictor of cardiovascular mortality and morbidity in AIS.