OBJECTIVES: The common international standard for measuring health benefit within economic evaluation requires the use of generic preference-based health-related quality of life (HRQoL) instruments. The availability of multiple instruments raises questions about their relative merits and recent studies have highlighted the paucity of evidence regarding measurement properties in the context of spinal cord injury (SCI). As part of a mixed-methods research program, this qualitative study explores the appropriateness of 6 established instruments for use in SCI populations. METHODS: Individuals living with SCI were invited to participate in one of three focus groups (n=15). Eligible participants were identified from Vancouver General Hospital’s Spine Program database; purposive sampling was used to ensure that a range of demographic and injury-related characteristics were represented. Perceptions and opinions were solicited on the following questionnaires: 15D, Assessment of Quality of Life (AQoL-8D), EQ-5D-5L, Health Utilities Index, self-administered Quality of Well-Being Scale, and SF-36v2. Framework Analysis was used to evaluate the qualitative information gathered during discussion. Strengths and limitations of each questionnaire were thematically identified and managed using NVivo software.  RESULTS: Major emergent themes were (i) general perceptions, (ii) comprehensiveness, (iii) content, (iv) wording, and (v) features. Two sub-themes pertinent to content were also identified; ‘questions’ and ‘options’. All focus group participants perceived the AQoL-8D to be the most relevant instrument to administer to an SCI population. This measure was widely considered to be comprehensive, with relevant content (i.e. wheelchair inclusive) and applicable items. Participants had mixed perceptions about the other 5 questionnaires, albeit to varying degrees.  CONCLUSIONS: The 35-item AQoL-8D was consistently viewed as the most appropriate preference-based HRQoL instrument for individuals living with SCI. Despite a strong theoretical underpinning, AQoL instruments are infrequently used in North America and further empirical research is necessary to build on these encouraging qualitative findings.