BACKGROUND: Autism entails reduced communicative abilities. Approximately 30% of individuals with autism have intellectual disability (ID). Some people with autism and ID are virtually non-communicative and unable to notify their caregivers when they are in pain. In a pilot study, we showed that heart rate (HR) monitoring may identify painful situations in this patient group, as HR increases in acutely painful situations. OBJECTIVES: This study aims to generate knowledge to reduce the number of painful episodes in non-communicative patients' everyday lives. We will 1) assess the effectiveness of HR as a tool for identifying potentially painful care procedures, 2) test the effect of HR-informed changes in potentially painful care procedures on biomarkers of pain, and 3) assess how six weeks of communication through HR affects the quality of communication between patient and caregiver. METHODS: We will recruit 38 non-communicative patients with autism and ID residing in care homes. ASSESSMENTS: HR is measured continuously to identify acutely painful situations. HR variability and pain-related cytokines (MCP-1, IL-1RA, IL-8, TGFß1, and IL-17) are collected as measures of long-term pain. Caregivers will be asked to what degree they observe pain in their patients and how well they believe they understand their patient's expressions of emotion and pain. Pre-intervention: HR is measured 8 h/day over 2 weeks to identify potentially painful situations across four settings: physiotherapy, cast use, lifting, and personal hygiene. INTERVENTION: Changes in procedures for identified painful situations are in the form of changes in 1) physiotherapy techniques, 2) preparations for putting on casts, 3) lifting techniques or 4) personal hygiene procedures. DESIGN: Nineteen patients will start intervention in week 3 while 19 patients will continue data collection for another 2 weeks before procedure changes are introduced. This is done to distinguish between specific effects of changes in procedures and non-specific effects, such as caregivers increased attention. DISCUSSION: This study will advance the field of wearable physiological sensor use in patient care. TRIAL REGISTRATION: Registered prospectively at ClinicalTrials.gov (NCT05738278).