OBJECTIVES: Drug utilisation studies (DUS) are increasingly requested by regulatory authorities and payers to evaluate the benefit-risk of drugs in real-life. DUS usually aim at evaluating off-label use, presence of contra-indicated concomitant drugs or comorbidity, appropriate monitoring, amongst others. In countries where no claims databases are available, such DUS involve the review of medical charts or pharmacy records. However, the ethical requirements pertaining to the conduct of DUS involving ad hoc data collection appears to be heterogeneous across countries and settings. The present study aims at defining the ethical and/or legal requirements applicable, within ICH countries, for the conduct of DUS in hospital and ambulatory care settings.  METHODS: Three strategies were used: (i) a review of existing legislative sources in the countries of interest; (ii) a review of the literature on DUS and extraction of information on ethical requirements; (iii) a survey sent to 125 ethics committees and/or key informants including case studies considering different types of data collection methods, study populations and care settings.  RESULTS: The literature review confirmed the great disparity across local legislation on DUS worldwide. Indeed, the ethical policies at the level of institutions are heterogeneous. Results from the survey revealed that most of the time, a site-specific ethics approval is required for DUS involving ad hoc data collection and that legislation related to data protection vary between countries. In addition, depending on the characteristics of the DUS, such requirements may differ. However, results also highlighted that, due to the lack of existing guidelines, most ethics committees refer to the Declaration of Helsinki regarding the ethical requirements applicable for DUS which suggests opportunities for harmonization.  CONCLUSIONS: The lack of consensus in the legislative and ethical framework for DUS across different countries highlights the operational challenges for the implementation of such studies, especially those involving multiple countries.