Background: Pharmacological treatment of tinnitus cannot be considered well established. Thus, reducing tinnitus severity through behavioral therapy is emerging as a key goal. Methods: A total of 286 patients suffering from persistent and stable tinnitus for four months or longer participated in this controlled clinical multicenter study. The study investigated the efficacy and safety of a standardized treatment involving individual cognitive-behavioral therapy (CBT). Controls were 120 patients waiting to be treated. Therapy was standardized using manualized procedures within the setting of a specifically designed disease management program. The primary outcome measure was the tinnitus change score using an 8-point numeric verbal rating scale. Secondary outcome measures were tinnitus severity as determined by the tinnitus questionnaire score as well as the tinnitus loudness score and the tinnitus annoyance score using 6- and 8-point numeric verbal rating scales, respectively. Following a significant multivariate rank test, these four validated outcome measures were tested in the order given. Results: The primary outcome measure, tinnitus change score, showed an efficacy of treatment with an odds ratio of 3.4 (95% confidence interval, 2.6-4.5). Of the treated patients, 84% showed a tinnitus change score improvement, but only 22% of controls did. The secondary outcome measures of tinnitus questionnaire score, loudness score, and annoyance score improved in the treatment group significantly more than in the control group. In the therapy group, the tinnitus questionnaire score was reduced by 50% from a median of 27 to 13.5; in the control group, no change in median tinnitus questionnaire score was observed. The multivariate endpoint of the primary and secondary outcome measures differed significantly (P < 0.0001) between treatment and control groups. The same was true when univariate scores were considered. Conclusions: A structured tinnitus-specific CBT using standardized tinnitus-specific interventions can be an effective individual therapy for the treatment of patients suffering from tinnitus for at least 4 months.The trial was registered at the ClinicalTrials.gov registry (ID: NCT 00719940).