Abstract. Depression is one of the most prevalent mental disorders, with treatment outcomes generally being unsatisfactory. The identification of outcome predictors could contribute to improving diagnosis, treatment, and outcome. Heart rate variability (HRV), an index of cardiovagal activity, has been proposed as a potential correlate of depression as well as a predictor of treatment effectiveness. The aim of the present study was to examine if HRV at baseline could predict the outcome of inpatient treatment for stress-related depressive disorder (SRDD). Depressive symptoms of n = 57 inpatients with an SRDD, who were treated in a specialized burnout ward, were assessed using the Beck Depression Inventory (BDI) at the beginning, the end of treatment, and at 3-month follow-up. HRV (i.e., RMSSD, the root mean square of successive RR interval differences) was determined from a five-minute measurement in the supine position. RMSSD was not significantly associated with the BDI score at the beginning, end, and follow-up. Higher RMSSD was revealed to be a significant predictor of a stronger decrease in depressive severity from the beginning to the end of the treatment. Thereby, the regression model explained 7.6% of the total variance in the BDI decrease. The results revealed initial HRV to predict a larger decrease in depressive severity. Therefore, resting HRV represents a physiological resource and index of successful neurovisceral interaction, which supports inpatients in benefitting from specialized treatment.