INTRODUCTION: Mechanical insufflation-exsufflation (MIE) is a commonly used therapy to augment secretion clearance in individuals with neuromuscular disease. There are no clear evidence-based guidelines on the settings that should be used in different diagnostic groups and how they should be titrated. We report on the settings used in the largest cohort of individuals using domiciliary MIE in the literature. METHODS: A retrospective observational study reporting on all individuals initiated on MIE for long-term domiciliary use at our centre, 2013-2019. RESULTS: This study reports on 359 adults established on domiciliary MIE. The most common diagnostic groups were congenital neuromuscular disease (26%), spinal cord injury (23%) and amyotrophic lateral sclerosis (23%). Median age at initiation was 55 years. Median (IQR) insufflation pressure was 35 (30-40) cm H CONCLUSION: This is the largest reported cohort of adults using domiciliary MIE. The most common groups using MIE were congenital neuromuscular disease, spinal cord injury patients and amyotrophic lateral sclerosis. The range of prescribed settings is narrow, reflecting the limited evidence base in this field and the need to better understand optimal targets for titration of different MIE settings.