OBJECTIVES: No specific health-related quality of life (HRQOL) instrument tool is available for Huntington’s disease (HD). In the context of a large European study on HD burden (Euro-HDB), a specific HRQoL tool (HQOLI) was created for patients in early and intermediate stages of HD. We describe the development and psychometric validation of HQOLI. METHODS: After semi-structured interviews with patients, caregivers and HD specialists, we ran a patient focus group. A self-reported questionnaire was then devised in French language. The questionnaire consists of 42 items, relating to 11 dimensions: Mobility, Motor Ability, Autonomy 1 and 2, Finance, Occupational Activities, Psychology, Feelings of Guilt, Vitality, Socializing and Body Image. Face validity, internal and external validity were examined. RESULTS: Among 178 participating patients, 15 did not complete HQOLI. Item response rates range from 0.81 to 0.98, excluding the occupational activities domain. As expected, there is a ceiling effect on several items, suggesting low sensitivity at advanced HD stage. Cronbach’s alphas are greater than 0.76. HQOLI total score is highly correlated with generic HR-QOL (SF36 and EQ5D) as well as with the specific caregiver HRQoL instrument (HDQoL-C). Correlations were -0.73 (p<0.01) with EQ5D utility, -0.76 (p<0.01) with ‘Physical Functioning’, -0.74 (p<0.01) with ‘Mental Health’. Voluntary movement, fall/balance and dystonia symptoms contribute significantly to HQOLI (p=0.01), but chorea does not (p=0.21). CONCLUSIONS: These data support the validity of the HQOLI in patients with HD. The ceiling effect limits the use of HQOLI in late stages but appears necessary to achieve good discrimination at early and intermediate stages. Correlations with other instruments suggest good external validity. High correlations of several items within dimensions suggest item number can be reduced. A new, shorter version of the questionnaire is in development.  Assessments of responsiveness to change, test–retest reliability and cross-cultural validation will be performed/are underway.