Background: A validated patient-reported outcome instrument is lacking for the functional dyspepsia/postprandial distress syndrome. Aim: To validate the Leuven Postprandial Distress Scale (LPDS). Methods: The LPDS diary, comprising eight symptoms with verbal descriptors rated for severity (0–4), was derived from focus groups and cognitive debriefing. It was used in a 2-week run-in, 8-week double-blind placebo-controlled trial of itopride 100 mg t.d.s. Results in 60 patients, with concealed treatment allocation, were used to analyse LPDS content validity, consistency, reliability and responsiveness. Patients also filled out Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM), Nepean Dyspepsia Index, overall treatment evaluation and overall symptom severity questionnaires. Construct validity was evaluated by known-group analyses and by correlating LPDS with these additional questionnaires. Minimum Clinically Important Difference was determined from threshold changes in anchor questionnaires. Results: Symptom patterns and factor analysis identified three cardinal symptoms of postprandial distress syndrome (early satiation, postprandial fullness, upper abdominal bloating), whose mean intensities generate weekly LPDS scores. Known-groups analysis showed large-effect-size differences in LPDS scores (Cohen's d = 2.16). Strong correlations (r > 0.57) between LPDS scores and relevant anchors at baseline indicate good convergent validity. Internal consistency of LPDS was good (α > 0.85) with high inter-item correlations (0.67–0.76), and test–retest reliability (r = 0.85). Changes in LPDS scores were highly convergent with changes in overall treatment evaluation, overall symptom severity and PAGI-SYM (r > 0.52). minimum clinically important difference analysis generated thresholds of 0.4-0.6. Conclusions: The Leuven Postprandial Distress Scale, which is supported by the European Medicines Agency, is a sensitive and reliable patient-reported outcome instrument to assess symptoms in the functional dyspepsia/postprandial distress syndrome. ; 13 page(s)