BACKGROUND Functional dyspepsia (FD) constitutes a complex picture with a variety of epigastric symptoms. No standard therapy is currently available for FD. OBJECTIVE This multicenter, placebo-controlled, double-blind study evaluated the efficacy and tolerability of the herbal drug STW 5, mainly comprising a fresh plant extract from Iberis amara. METHODS Patients with FD were included. Gastrointestinal endoscopy, H. pylori-status, and a 7-day run-in phase were required. A total of 315 patients were treated with 3 x 20 drops/day of either STW 5 or placebo. Symptom assessment: day 0, 2, 4, and 8 wk of treatment. The principal outcome criterion was the change in a validated Gastrointestinal Symptom Score (GIS). Symptom severity was rated using the Likert scale. RESULTS A total of 315 patients remained in the safety population. Of them, 158 were treated with STW 5 and 157 with placebo. The intention-to-treat population comprised 308 patients. Dropout number was similar in both groups. GIS showed improvement during the treatment period. The STW 5 group improved 6.9+/-4.8 points up to day 56, placebo group by 5.9+/-4.3 (P<0.05). H. pylori did not influence the results. Drug tolerability and safety were similar in both groups. CONCLUSIONS This placebo-controlled study with an 8-wk treatment period documents the efficacy of STW 5 in FD.