We treated 33 cases of intractable Meniere's disease with endolymphatic sac drainage and steroid-instillation surgery (EDSS), attaining good long-term results in vertigo and hearing. To elucidate how EDSS affects the diseased inner ear, we examined changes in plasma inner ear hormones after EDSS. Among inner ear hormones, plasma vasopressin was significantly decreased after EDSS compared to after mastoidectomy. In cases with good long-term results in vertigo and hearing, postoperative plasma vasopressin remained lower over the long term than in cases with poor results. In cases with negative glycerol test results one year after surgery, postoperative plasma vasopressin also remained significantly lower over the long term than in cases with positive results. Previous studies reported that vestibular neurons projected into hypothalamic supraoptic and paraventricular nuclei and that changes in the inner ear pressure were related to plasma vasopressin. Taken together with present findings, this suggests that EDSS may reduce plasma vasopressin through modification of the diseased inner ear environment, resulting in improved inner ear function.