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Gillian E Caughey,1,2 Kirsty Tait,3 Agnes I Vitry,3 Sepehr Shakib2,4 1Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, 2Department of Clinical Pharmacology, Royal Adelaide Hospital, 3School of Pharmacy and Medical Sciences, University of South Australia, 4Discipline of Pharmacology, School of Medicine, University of Adelaide, North Terrace, Adelaide, SA, Australia Abstract: Multimorbidity is associated with use of multiple medicines, increased risk of adverse events and treatment conflicts. This study aimed to examine how older patients with multimorbidity and clinicians balance the benefits and harms associated with a medication and in the presence of competing health outcomes. Interviews were conducted with 15 participants aged ≥65 years with 2 or more chronic conditions. Three clinical scenarios were presented to understand patient preference to take a medicine according to i) degree of benefit, ii) type of adverse event and impact on daily living and iii) influence of comorbid conditions as competing health outcomes. Semi-structured interviews were also conducted with participants (n=15) and clinicians (n=5) to understand patient preferences and treatment decisions, in the setting of multimorbidity. The median age of participants was 79 years, 55% had 5 or more conditions and 47% took 8 or more medicines daily. When the level of benefit of the medicine ranged from 14% to 70%, 80% of participants chose to take the medicine, but when adverse effects were present, this was reduced to 0–33% depending upon impact on daily activities. In the presence of competing health outcomes, 13%–26% of patients chose to take the medicine. Two-thirds of patients reported that their doctor respects and considers their preferences and discussed medication benefits and harms. Interviews with clinicians showed that their overall approach to treatment decision-making for older individuals with multimorbidity was based upon 2 main factors, the patients’ prognosis and their preferences. The degree of benefit gained was not the driver of patients’ preference to take a medicine; rather, this decision was influenced by type and severity of adverse effects. Inclusion of patient preferences in the setting of risks and benefits of medicines with consideration and prioritization of competing health outcomes may result in improved health outcomes for people with multimorbidity. Keywords: multimorbidity, comorbidity, patient preference, patient decision-making, medicines, geriatrics