BACKGROUND AND OBJECTIVE: Despite the availability of successful treatment approaches for chronic tinnitus, it has proven difficult to predict who profits from treatment and it is still an open question if it is possible at all. We tried to overcome methodological shortcomings and to predict treatment outcome indicated by questionnaires measuring tinnitus distress. METHODS: This is an observational, prospective cohort study. Lasso and post-selection inference methods were used to predict treatment outcome in patients suffering from chronic tinnitus (N = 747). Patients were treated for five consecutive days in an interdisciplinary setting according to guidelines. RESULTS: Early change, i.e. a positive response after the screening day, as well as change due to treatment was predicted by several psychopathological variables, but also tinnitus-related factors. Female gender as an example was a predictor for change due to treatment. In general, therapy success both for early change and change due to treatment cannot be predicted satisfactorily as indicated by a high mean cross-validation error (for early change: 9.83, for change due to treatment: 14.40). Analyzing sub-groups separated by tinnitus severity to reduce heterogeneity did not improve the situation and for patients with high tinnitus severity no predictors at all could be reported (cross-validated error: 11.62 for the low quartile, 13.38 for the low-medium quartile, and 15.61 for the medium-high quartile). CONCLUSION: Several psychopathological and tinnitus-related variables predicted early and long-term change. Nevertheless, also overcoming methodological shortcomings to predict treatment success did not lead to satisfactory results, but rather emphasizes the high heterogeneity of chronic tinnitus.