The association between adiponectin, leptin, and resistin and the long-term outcome of ischemic stroke are controversial. We aimed to evaluate this relationship. We prospectively studied 83 patients consecutively hospitalized for acute ischemic stroke (38.6% males, age 79.7 ± 6.3 years). Serum adiponectin, leptin, and resistin levels and the -420C > G polymorphism of the resistin gene were determined at admission. Stroke severity at admission was evaluated with the National Institutes of Health Stroke Scale (NIHSS). One year after discharge, functional status, incidence of cardiovascular events and all-cause mortality were recorded. Functional status was evaluated with the modified Rankin scale (mRS). Patients with the G allele had lower mRS ( < .05) and patients with adverse outcome had higher serum resistin levels ( < .05). The only independent predictor of adverse outcome was mRS at discharge (risk ratio (RR) 2.78, 95% confidence interval (CI) 1.54-5.00;  < .001). Higher adiponectin levels were an independent predictor of cardiovascular morbidity (RR 1.07, 95% CI 1.01-1.14;  < .05). Patients who died had higher serum adiponectin levels than those who survived ( < .05). The only independent predictor of all-cause mortality was NIHSS at admission (RR 1.19, 95% CI 1.04-1.35;  < .01). In patients with acute ischemic stroke, the G allele of the -420C > G polymorphism of the resistin gene promoter is more frequent in those with a more favorable functional outcome at one year after discharge. Patients with higher serum resistin levels appear to have worse long-term functional outcome, while higher serum adiponectin levels are associated with higher incidence of cardiovascular events.