OBJECTIVE: To evaluate efficacy and safety of memantine in the treatment of tinnitus. STUDY DESIGN: Prospective, randomized, double-blind crossover study. SUBJECTS AND METHODS: A total of 60 patients with tinnitus were randomized into a double-blind, placebo-controlled, prospective crossover study. Patients each received up to 20 mg memantine and placebo for 90 days, separated by a 30-day washout period. Treatment effects were assessed by using the Tinnitus Handicap Inventory (THI). A total of 43 patients completed the trial. RESULTS: There was no significant improvement of THI score after memantine treatment compared with placebo. A possible tendency for delayed effects of memantine was observed. The incidence of side effects during memantine treatment was 9.4 percent, leading to interruption of treatment in all cases. CONCLUSION: This study does not provide evidence to recommend memantine for the treatment of tinnitus. A possible late effect of the drug should be evaluated in further studies with longer observation periods.