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Introduction: Multimorbidity is a major challenge for current healthcare systems and professionals. From the different approaches that have been proposed to analyse this issue, the hypothesis of the existence of association patterns of different chronic conditions is gaining visibility. In addition, multimorbidity can be associated to polypharmacy, which can lead to a higher risk of potentially inappropriate prescribing (PIP) and consequently to adverse drug reactions (ADRs). The general objective of this novel study is to identify the association between PIP, multimorbidity patterns, polypharmacy and the presence of ADRs in older patients admitted for exacerbation of chronic diseases., Methods and Analysis: The MoPIM (morbidity, potentially inappropriate medication) study is a multicentre prospective cohort study of an estimated sample of 800 older (≥65 years) patients admitted to five general hospitals in Spain due to an exacerbation of a chronic disease. Patients referred to home hospitalisation, admitted due to an acute process or with a fatal outcome expected at the time of admission are excluded. Sociodemographic data, chronic morbidities and geriatric syndromes, number of chronic prescribed medications, PIP at admission to hospital and on discharge, according to the newest screening tool of older screening tool of older person's potentially inappropriate prescriptions/screening tool to alert doctors to right treatment criteria, and ADRs during hospitalisation are being collected. Multimorbidity patterns will be identified using cluster analyses techniques, and the frequency of polypharmacy, PIP and ADRs will be calculated. Finally, the possible relationship between those indicators will be identified through bivariate and multivariate analyses., Ethics and Dissemination: The project has been approved by the clinical research ethics committees of each centre: Comité Ético de investigación Clínica del Parc Taulí, Comitè Ètic d'Investigació Clínica Osona per a la Recerca i Educació Sanitàries (FORES), Comité de Ètica de la Investigación con Medicamentos (CEIm)-Parc de Salut MAR, Comité Ético de Investigación Clínica de Euskadi, Comité de Ética de Investigación del Hospital Universitario de Canarias. The results will be actively and mainly disseminated through publication in peer-reviewed journals and communications in scientific conferences., Trial Registration Number: NCT02830425., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)