The objective of this study was to contribute evidence regarding the use of the SF6D and HUI3 in persons with neurological conditions. The data of 776 individuals from the LINC Study was analyzed. The mean utility score of the HUI3 was 0.47 (95% CI 0.45, 0.49) and SF6D was 0.62 (95% CI 0.62, 0.63). Even though the SF6D and HUI3 were sensitive to a variety of HRQoL domains relevant to persons with neurological conditions, they showed only marginal agreement (ICC of 0.41) with a mean utility difference of 0.15 (95% CI 0.13, 0.17). Discordance varied systematically with HRQoL status and was consistent regardless of the participant or impairment characteristics present. Despite sharing a common purpose, the substantial and clinically important differences found between the SF6D and HUI3 cast doubt on whether the utility estimates produced by these instruments are directly comparable or universally valid.