Background Mitochondrial diseases in adults are generally chronic conditions with a wide spectrum of severity contributing to disease burden and healthcare resource utilisation. Data on healthcare resource utilisation in mitochondrial diseases are limited.Objectives We performed a retrospective longitudinal study to investigate the clinical drivers of hospitalisation in adult patients with mitochondrial diseases to better understand healthcare resource utilisation.Methods We recruited participants from our specialised Mitochondrial Disease Clinic in Sydney, Australia between September 2018 and December 2021. We performed a retrospective chart review for the period 2013–2022 considering emergency department (ED) and/or hospital admission notes, as well as discharge summaries. We used multiple linear regression models to examine the association between the type of presenting symptom(s) and duration of hospital stay and frequency of admissions, while adjusting for relevant covariates.Results Of the 99 patients considered, the duration of hospitalisation ranged from 0 to 116 days per participant and the number of admissions ranged from 0 to 21 per participant. Participants with one or more mitochondrial disease-associated admissions constituted 52% of the study cohort. 13% of the participants presented to the ED without requiring an admission and 35% never attended the ED or required a hospital admission during this period. Neurological (p