Abstract Context There is evidence that portable high-efficiency-particulate-air (HEPA) filtration units remove microbial particles from the air, but it is unclear whether this is sufficient to reduce infections in care home residents. Objectives To investigate the effectiveness of portable HEPA filtration units for winter respiratory infection episode reduction in care home residents. Study design and analysis: Cluster controlled trial with intention-to-treat analysis. Setting: 90 residential care homes for older adults in England. Population: Residents expected to reside in the care home for ≥1 month. Intervention care homes: Five HEPA filtration units in communal rooms and one HEPA filtration unit in 10 to 16 bedrooms. Control care homes: Usual care. Outcome measures: The primary outcome is the number of symptomatic winter respiratory infection episodes recorded by care home staff. Secondary outcomes: other infection measures; falls /near falls; laboratory confirmed infections; hospitalisations; and staff sickness. Process evaluation to assess intervention acceptability and implementation. Results Care homes were randomised between January 2022 and February 2024, 43 to intervention and 47 to usual care. Respectively, in intervention and control group care homes: 43% and 45% provided nursing care; 87% and 87% dementia care; and median (IQR) number of communal rooms were 4 (3-5) in both groups. 1126 residents were consented, of whom 31 (3%) moved away; 151 (13%) died; and 5 stopped participating. Primary outcome data is 98% complete with 175,318 'resident days' symptom data collected. Comparing intervention and control group residents: median (IQR) age was 88 (81-92) and 88 (82-92) years; 33% and 43% were receiving nursing care; 58% and 57% had dementia; frailty scores were 6 (4-7) and 6 (5-7); 94% and 94% received influenza; and 97% and 95% COVID vaccines. Conclusions Final analytic results of this world-first RCT will be available for the conference. Key messages • This world-first RCT using HEPA filters in care homes will report the evidence of effectiveness of respiratory infection episode reduction in care home residents. • The trial will inform policy makers about the effectiveness, acceptability and implementation of HEPA filters in care homes.