Introduction: Home enteral nutrition (HEN) is indicated in patients with a functional gastrointestinal tract but who are unable to meet their nutritional requirements with normally consumed foodstuffs. HEN allows patients to remain in their social and family environment, thus reducing complications and costs associated with hospital admission, while increasing health-related quality of life (HRQoL). HRQoL in patients with HEN is mainly evaluated by generic instruments, which are not sensitive enough to identify certain specific patient-related outcomes of HEN. Objective: To develop a specific instrument to measure HRQoL in patients receiving HEN whose results allow interpretation regardless of the underlying disease and nutritional support administration route: the NutriQoL (R) questionnaire. Materials and methods: The development of the NutriQoL entailed a literature review, focus groups with experts, semistructured interviews with patients, an assessment of face validity and feasibility, and Rasch analysis conducted on data from a sample of 141 patients and 24 caregivers. Results: Of the 52 items initially proposed on the basis of the literature review, expert focus group, and semi-structured interviews with patients and caregivers, 17 items were finally selected through the development process to make up the final version of the NutriQoL, as well as a visual analog scale for global HRQoL scoring. The selected items were evaluated as adequate for frequency, importance, and clarity. Furthermore, they have been shown to be independent of the underlying condition and HEN administration route. Conclusion: A new instrument for measuring the HRQoL of patients with HEN in Spain has been developed, whose results are independent of the underlying condition and administration route. The next step will be the validation of the questionnaire to ensure that the instrument is valid, reliable, and sensitive to health status changes in patients, to be used periodically in usual clinical practice.