OBJECTIVES: Following the 2009 FDA Guidance, a new PRO instrument was developed to support endpoints in multinational clinical trials assessing IBS with diarrhea (IBS-D) symptom severity. Our objective was to assess the translatability of the IBS-D PRO instrument into ten languages, and subsequently perform a cultural adaptation/linguistic validation of the questionnaire into US Spanish and Japanese.] METHODS: Translatability assessments of the US English version of the IBS-D PRO were performed by experienced PRO translators who were native speakers of each target language and currently residing in-country. Languages included: Chinese (China); Dutch (Netherlands); French (Belgium); German (Germany); Japanese (Japan); Polish (Poland); Portuguese (Brazil); Russian (Russia); Spanish (Mexico); and Spanish (US). The project team assessed the instrument to identify potential linguistic and/or cultural adaptation issues. After the identified issues were resolved, the instrument was translated into Spanish (US) and Japanese through a process of two forward translations, one reconciled translation, and one back translation. The project team reviewed the translated versions before the instruments were evaluated by cognitive debriefing interviews (CDIs) with samples of five Spanish (US) and five Japanese IBS-D patients. RESULTS: A few linguistic and cultural adaptation concerns were identified during the translatability assessment as requiring minor revisions: mainly the presentation of dates/times and word structure. During the CDIs, two out of five Spanish respondents misunderstood the term “bowel movement” to mean only diarrhea in the Spanish version. Consequently, the term was changed from “movimiento intestinal” to “evacuaciones.” None of the Japanese respondents identified issues with the Japanese version. CONCLUSIONS: The translatability of the IBS-D PRO instrument into ten target languages was confirmed, with only minor changes made to the translations of the instrument. The translation and linguistic validation into Spanish (US) and Japanese provide evidence that this instrument can be used in multinational trials and clinical settings.