Acquired and congenital syphilis are both known causes of potentially reversible sensorineural hearing loss. Various therapeutic regimens, including penicillin and/or corticosteroids have been used in the past as treatment for otosyphilis. Response rates have varied from 15% to 80%. In this retrospective study, 13 patients with otosyphilis were treated with a combined course of long-term penicillin and prednisone. A significant response was defined as a 15% improvement in the discrimination score and/or the pure tone average. Initial response rates were 35% with a lasting response rate of 15%. Discrimination scores improved more commonly than pure tone averages. No patient with congenital syphilis or profound deafness had a lasting response. An analysis of possible reasons for failure of therapy is discussed.