OBJECTIVES: To show how translatability assessment during the patient-reported outcome (PRO) measure development process can be used to identify areas where wording changes are needed to improve and refine the measure. METHODS: A translatability assessment was conducted on a new 35-item PRO measure called Symptoms of Major Depressive Disorder (S-MDD) for evaluating treatment benefits in MDD.  Five different languages were selected (French, Spanish, German, Chinese, and Russian). Each PRO item was reviewed and assigned a difficulty rating between 1 (no difficulty) and 5 (extreme difficulty) by an experienced translation consultant in each language. The difficult concepts for translation were compared to the problematic items for patient comprehension (from cognitive interviews) to identify difficult items for both translation and patient comprehension. RESULTS: Three items of the 35-item S-MDD showed difficulty in patient comprehension and in the ability to accurately translate the concept. Due to the convergence of these two problematic findings during the PRO development, the item “how difficult was it for you to keep your mind free of worrying thoughts?” was changed to “how difficult was it for you to stop thinking about your problems?”  The item “how much have you looked forward to things with enjoyment?” was changed to “how much of the time did you feel enjoyment?”, and “how much have you felt useful?” was revised to read “how much of the time did you feel useful?” CONCLUSIONS: When translatability assessment is conducted prior to the finalization of a new measure, language changes can be implemented that will facilitate translation and cross cultural adaptation.  When difficulties are encountered that may not warrant changes on their own, results from translatability assessments  can also be useful in adding awareness and greater weight to other aspects of item structure that might need to be altered to improve the integrity and quality of the measure.