The clinical associations of the anti-ganglionic acetylcholine receptor (gAChR) have not yet been described fully. It is not known whether central nervous system (CNS) involvement and endocrine disorders are the extra-autonomic features of autoimmune autonomic ganglionopathy (AAG), or whether it is related to circulating anti-gAChR antibodies (Abs). The present study prospectively identified 123 Abs-positive AAG patients in Japan and collated their clinical features, investigations, and immunotherapy responses. Luciferase immunoprecipitation systems were used to detect anti-α3 and -β4 gAChR Abs. A gradual mode of onset was more common among the 123 seropositive AAG patients examined. Patients with AAG demonstrated widespread autonomic dysfunction. In particular, orthostatic hypotension and lower gastrointestinal tract dysfunction were frequently observed. Approximately 80% of patients with seropositive AAG exhibited extra-autonomic manifestations, including CNS involvement, endocrine disorders, other autoimmune disease, and tumors. Additionally, the majority exhibited a marked improvement in clinical status and the levels of anti-gAChR Abs with immunotherapy. CNS involvement and endocrine disorders were frequent among the seropositive patients with AAG, indicating that seropositivity for AAG may be associated with underlying conditions such as autoimmune diseases or tumors.