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Objectives: The increasing incidence of multiple sclerosis (MS) worldwide, especially in women, points to the crucial role of environmental and lifestyle risk factors in determining the disease occurrence. An international multicentre case-control study of Environmental Risk Factors In Multiple Sclerosis (EnvIMS) has been launched in Norway, Sweden, Italy, Serbia and Canada, aimed to examine MS environmental risk factors in a large study population and disclose reciprocal interactions. To ensure equivalent methodology in detecting age-related past exposures in individuals with and without MS across the study sites, a new questionnaire (EnvIMS-Q) is presented., Materials and Methods: EnvIMS-Q builds on previously developed guidelines for epidemiological studies in MS and is a 6-page self-administered postal questionnaire. Participants are de-identified through the use of a numerical code. Its content is identical for cases and controls including 'core' and population-specific questions as proxies for vitamin D exposure (sun exposure, dietary habits and supplementation), childhood infections (including infectious mononucleosis) and cigarette smoking. Information on possible confounders or effect modifiers is also obtained. EnvIMS-Q was initially drafted in English and subsequently translated into Italian, Serbian, Norwegian, Swedish and French-Canadian. EnvIMS-Q has been tested for acceptability, feasibility and reliability., Results and Conclusions: EnvIMS-Q has shown cross-cultural feasibility, acceptability and reliability in both patients with MS and healthy subjects from all sites. EnvIMS-Q is an efficient tool to ensure proper assessment of age-specific exposure to environmental factors in large multinational population-based case-control studies of MS risk factors., (© 2012 John Wiley & Sons A/S.)