A multicentric noninterventional trial (open study without control) to investigate the efficacy and tolerance of a drug in a large number of patients under routine medical conditions was performed for a new solid preparation from an extract of the fruit of Vitex agnus castus (VAC, Vitex, chaste tree, Chasteberry) in 1634 patients suffering from premenstrual syndrome (PMS). A specific questionnaire was developed for determining the effect of Vitex on psychic and somatic complaints, on the four characteristic PMS symptom complexes depression, anxiety, craving, and hyperhydration (DACH), and on single groups of symptoms. After a treatment period of three menstrual cycles 93% of patients reported a decrease in the number of symptoms or even cessation of PMS complaints. To a certain extent, this effect was observed within all symptom complexes and correlated with the global assessment of therapeutic efficacy. Whereas 85% of physicians rated it as good or very good, 81% of patients assessed their status after treatment as very much or much better. Analysis of frequency and severity of mastodynia as the predominant symptom revealed that complaints still present after 3 months of therapy were mostly less severe. Ninety-four percent of patients assessed the tolerance of Vitex treatment as good or very good. Adverse drug reactions were suspected by physicians in 1.2% of patients, but there were no serious adverse drug reactions. Hence, the risk/benefit ratio of the new Vitex preparation can be rated as very good, with significant efficacy for all aspects of the multifaceted and inhomogeneous clinical picture of PMS, with a safety profile comparable to other Vitex preparations.