Summary Background The Confidential Inquiry into premature deaths of people with intellectual disabilities in England was commissioned to provide evidence about contributory factors to avoidable and premature deaths in this population. Methods The population-based Confidential Inquiry reviewed the deaths of people with intellectual disabilities aged 4 years and older who had been registered with a general practitioner in one of five Primary Care Trust areas of southwest England, who died between June 1, 2010, and May 31, 2012. A network of health, social-care, and voluntary-sector services; community contacts; and statutory agencies notified the Confidential Inquiry of all deaths of people with intellectual disabilities and provided core data. The Office for National Statistics provided data about the coding of individual cause of death certificates. Deaths were described as avoidable (preventable or amenable), according to Office for National Statistics definitions. Contributory factors to deaths were identified and quantified by the case investigator, verified by a local review panel meeting, and agreed by the Confidential Inquiry overview panel. Contributory factors were grouped into four domains: intrinsic to the individual, within the family and environment, care provision, and service provision. The deaths of a comparator group of people without intellectual disabilities but much the same in age, sex, and cause of death and registered at the same general practices as those with intellectual disabilities were also investigated. Findings The Confidential Inquiry reviewed the deaths of 247 people with intellectual disabilities. Nearly a quarter (22%, 54) of people with intellectual disabilities were younger than 50 years when they died, and the median age at death was 64 years (IQR 52–75). The median age at death of male individuals with intellectual disabilities was 65 years (IQR 54–76), 13 years younger than the median age at death of male individuals in the general population of England and Wales (78 years). The median age at death of female individuals with intellectual disabilities was 63 years (IQR 54–75), 20 years younger than the median age at death for female individuals in the general population (83 years). Avoidable deaths from causes amenable to change by good quality health care were more common in people with intellectual disabilities (37%, 90 of 244) than in the general population of England and Wales (13%). Contributory factors to premature deaths in a subset of people with intellectual disabilities compared with a comparator group of people without intellectual disabilities included problems in advanced care planning (p=0·0003), adherence to the Mental Capacity Act (p=0·0008), living in inappropriate accommodation (p<0·0001), adjusting care as needs changed (p=0·009), and carers not feeling listened to (p=0·006). Interpretation The Confidential Inquiry provides evidence of the substantial contribution of factors relating to the provision of care and health services to the health disparities between people with and without intellectual disabilities. It is imperative to examine care and service provision for this population as potentially contributory factors to their deaths—factors that can largely be ameliorated. Funding Department of Health for England.