OBJECTIVE: To investigate the efficacy and safety of open-label placebos (OLP) in premenstrual syndrome (PMS). DESIGN: Randomised controlled trial. SETTING: Switzerland, 2018-2020. PARTICIPANTS: 150 women (18-45 years of age) with PMS or premenstrual dysphoric disorder. INTERVENTION: Random assignment (1:1:1) to treatment as usual (TAU), OLP without treatment rationale (OLP-), or OLP with treatment rationale (OLP+). OLP consisted of two placebo pills per day for 6 weeks. MAIN OUTCOME MEASURES: Primary outcomes were PMS symptom intensity and interference between groups across three menstrual cycles (MC1-MC3); adverse events (ie, safety) were measured at weeks 3 and 6 after the start of the intervention. Secondary outcomes were psychological and somatic subscales of PMS symptom intensity, and adherence. RESULTS: From 2 August 2018 to 3 December 2020,