OBJECTIVES: The Epworth Sleepiness Scale (ESS) is a self-administered questionnaire with eight questions, providing a measure of a person’s general level of daytime sleepiness, or their average sleep propensity in daily life. The ESS asks people to rate, on a 4-point scale (0 – 3), their usual chances of dozing off or falling asleep in eight different situations or activities that most people engage in as part of their daily lives (e.g., sitting, reading, watching TV, etc.). Situations differ in their somnificity, or sleep-inducing characteristics. The objective of this study is to present the challenges faced during the translation of the ESS into 66 different languages representing nine language families. METHODS: The ESS was translated following a methodology in compliance with the ISPOR guidelines. For most of the languages, the process consisted of: 1) Concept definition with the developer 2) Forward/backward translation step; 3) Final reconciliation; 5) Clinician review; 6) Cognitive interviews with five subjects. The Adjusted Process was used for countries using a national variant of the same language. RESULTS: Most of the situations or activities described in the ESS were easily translated and culturally relevant. Only item 7 (Sitting quietly after a lunch without alcohol) raised a lot of discussion in 46 languages either for cultural or syntactic/semantic or all reasons. In eight languages (e.g., used in countries like India, Malaysia or Israël), “without alcohol” was put between brackets since consumption of alcohol is not encouraged for cultural reasons. In 29 languages, verbs or periphrasis clarifying the meaning of “without alcohol” were used (e.g., without “drinking”, “using”, or “taking” alcohol). In 11 languages, “alcohol” was replaced by equivalents meaning “alcoholic beverage(s)” or “wine, beer or other alcoholic beverages” or “alcoholic drinks.” CONCLUSIONS: The rigorous methodology used was essential in producing ESS translations conceptually equivalent to the Australian English original.