To evaluate outcomes of intratympanic (IT) dexamethasone and gentamicin in Ménière Disease (MD).Charts of adult patients with unilateral definite MD receiving IT gentamicin or dexamethasone from 2005 to 2017 were retrospectively reviewed. All patients had at least 6 months follow-up. Failure in each group was defined as the need for more aggressive therapy. Prior to 2011, all patient received IT gentamicin, administered as primary therapy after failure of conservative treatment measures. Gentamicin was administered every 2 weeks, up to three injections, until vertigo control was achieved. Beginning in 2011, the treatment protocol shifted to IT dexamethasone as initial treatment, with gentamicin used for dexamethasone failures. Dexamethasone was administered weekly for up to three injections. Treatments could be repeated if symptoms recurred.Thirty-three patients received IT dexamethasone, and 70 patients received IT gentamicin. Dexamethasone patients received a mean of 3.3 injections compared to 2.7 in the gentamicin group (P = 0.011). There were 12 (38%) failures in the dexamethasone group and only seven (10%) gentamicin failures (P = 0.025). No patients failed both treatments. The mean time to failure in the dexamethasone group was 5 months, whereas in the gentamicin group it was 27 months. Change in pure tone audiometry from baseline was not different between treatment groups (P = 0.30).Subjects receiving IT gentamicin required fewer injections and had a significantly longer time to failure than IT dexamethasone. Audiometric outcomes were similar between the groups. The use of IT gentamicin as initial therapy for early and long-term control of MD is safe and effective.3 Laryngoscope, 129:216-221, 2019.