The trial was conducted to investigate the therapeutic effects and safety of a 4 week treatment with Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms. This was a multicentre, non-randomized, open-label, single-arm trial. One hundred and one subjects were enrolled in this clinical study and received the study drug at a dose of 200 mg twice daily for 4 weeks. Assessments with seven questionnaires included Numerical Analogue Scales of Subjective Stress Symptoms, Perceived Stress Questionnaire, Multidimensional Fatigue Inventory 20, Numbers Connecting Test, Sheehan Disability Scale and Clinical Global Impressions to cover various aspects of stress symptoms and adverse events. Invariably, all tests showed clinically relevant improvements with regard to stress symptoms, disability, functional impairment and overall therapeutic effect. Improvements were observed even after 3 days of treatment, as were continuing improvements after 1 and 4 weeks. Rhodiola rosea extract WS® 1375 was safe and generally well tolerated. Adverse events were mostly of mild intensity and no serious adverse events were reported. Rhodiola extract at a dose of 200 mg twice daily for 4 weeks is safe and effective in improving life-stress symptoms to a clinically relevant degree. Copyright © 2012 John Wiley & Sons, Ltd.