Objectives: Investigate the therapeutic efficacy of intratympanic dexamethasone after high-dose systemic corticosteroids in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: Prospective clinical trial at a university hospital. A total of 104 eligible patients with ISSNHL were treated consecutively. Patients in the severe group (>70 dB) were treated with intravenous high-dose prednisolone (500 mg per day, 5 days), whereas the rest were treated with oral deflazacort (1 mg per kg per day, 10 days). Failures after 5 days of systemic treatment received an additional 3 intratympanic dexamethasone injections. Results: The differences between pretreatment and posttreatment pure-tone audiometry averages (PTAs). Complete recovery was defined as PTA better than 25 dBs. Successful treatment was defined as a greater than 10 dB improvement in PTA. Results: Complete hearing recovery was achieved in 38 cases (36.53%), and significant hearing recovery in 86 cases (82.69%). After intravenous treatment of severe cases (initial PTA 83.15 dB), a median improvement of 13.61 dB was achieved; rescue intratympanic treatment obtained 18.49 dB of further improvement (final PTA 53.05 dB). Those less severe cases (initial PTA 68.38 dB) had a median improvement of 3.39 dB after oral treatment, and 9.00 dB after rescue (final PTA 56.00 dB). High-dose treatment in severe cases showed a significant improvement compared with the less severe group ( P < .01). Conclusions: High-dose intravenous corticosteroid treatment obtained significant hearing improvement in severe ISSNHL. The addition of intratympanic steroids to the conventional systemic steroid therapy may provide a safe and potentially effective therapeutic option.