Background: To evaluate the efficacy of a multidisciplinary stress treatment programme. Methods: General practitioners referred 198 employed patients on sick leave with symptoms of persistent work-related stress. Using a waitlisted randomised controlled trial design, the participants were randomly divided into the following three groups: the intervention group (IG, 69 participants); treatment-as-usual control group (TAUCG, 71 participants), which received 12 consultations with a psychologist, and the waitlisted control group (WLCG, 58 participants). The stress treatment intervention consisted of nine 1-hour sessions conducted over 3 months. The goals of the sessions were the following: (1) identifying relevant stressors; (2) changing the participant's coping strategies; (3) adjusting the participant's workload and tasks, and (4) improving workplace dialogue. Each participant also attended a mindfulness-based stress reduction (MBSR) course for 2 h a week over 8 weeks. Results: The IG and TAUCG showed significantly greater symptom level (Symptom Check List 92) reductions compared to the WLCG. Regarding the return to work (RTW) rate, 67% of participants in the IG returned to full-time work after treatment, which was a significantly higher rate than in the TAUCG (36%) and WLCG (24%). Significantly more participants in the IG (97%) increased their working hours during treatment compared with the participants in the control groups, TAUCG (71%) and WLCG (64%). Conclusions: The stress treatment programme - a combination of work place-focused psychotherapy and MBSR - significantly reduced stress symptom levels and increased RTW rates compared with the WLCG and TAUCG.