The aim of this study was to compare the effectiveness of work-related cognitive–behavioral treatment (W-CBT) with that of cognitive–behavioral treatment as usual (CBT-AU) for employees on sick leave as a result of a major depressive disorder (MDD). We collected data for 26 matched outpatients at pre- and posttreatment, as well as at 1-year follow-up. Outcome measures were the days of incapacity to work (DIW) as well as self-report measures (Beck Depression Inventory [BDI], Symptom Checklist 90-R [GSI], Life Satisfaction Questionnaire [FLZ]). We analyzed data with hierarchical linear modeling in a 2-level model. Therapy effects were defined in 3 ways: effect size (ES), response (based on the reliable change index), and remission compared with the general population's symptom level. The DIW were reduced significantly after both types of treatment, but employees showed even fewer DIW after W-CBT. At follow-up, significantly more employees were working as a result of W-CBT than with CBT-AU. Significant improvements on scores of self-rating measures corresponded with moderate-to-large effect sizes for both treatment types. Approximately 2 thirds of the treated employees were categorized as unimpaired on BDI scores at posttreatment and at follow-up. At least 1 half of the employees were classified as unimpaired on GSI scores at both assessment points. In future research, a randomized controlled trial should be conducted using a larger sample size to investigate the impact of moderators (e.g., employees at different branches of the company). Findings provided support for using common CBT techniques to enhance return to work without losing expected improvements at the symptom level.