OBJECTIVES: This study is a head-to-head comparison of the EuroQoL-five-dimensions questionnaire (EQ-5D-3L) and the Short Form-6-dimensions questionnaire (SF-6D) among MS caregivers.  Domain- and scale-level agreement between the measures was assessed.  Determinants of discordance in estimates were also identified. METHODS: A cross-sectional, descriptive design was employed. An online survey was administered to MS caregivers in the United States (US).  The distribution of EQ-5D-3L and SF-6D scores were examined graphically and via formal tests of normality.  Domain-level agreement was assessed using correlation coefficient.  Scale-level agreement was evaluated using an Intraclass correlation coefficient (ICC) and Bland-Altman plot.  Mean utilities were compared using a paired t-test.  Factors affecting discordance between EQ-5D-3L and SF-6D utility scores were ascertained using multivariable linear regression. RESULTS: The EQ-5D-3L generated a mean utility of 0.83 (±0.17) and a range of -0.04 to 1.00.  The SF-6D had a mean utility of 0.74 (±0.14) and a range of 0.345 to 1.00.  Discernable differences between utility distributions were noted.  Shapiro Wilk’s tests indicated departures from normality for both measures.  Strong correlation was observed between related domains of EQ-5D-3L and SF-6D, indicating domain-level agreement.  The mean difference in utility scores was 0.09 (±0.15).  An ICC of 0.46 indicated a fair level of agreement.  Wide limits of agreement in the Bland-Altman plot suggested poor agreement between the measures.  Caregiver marital status (β = –.129), family annual income (β = 0.159), and care recipient disability status (β = –.065) were significant predictors of discordance between two measures.   CONCLUSIONS: This is the first comparison of utility measures among MS caregivers.  The results reveal significant differences in EQ-5D-3L and SF-6D utilities.  Although both measures appear to assess similar domains, there was a lack of agreement was observed.  Meaningful differences between the measures suggest that EQ-5D-3L and SF-6D may not be used interchangeably in economic evaluations for interventions/treatments specific to MS caregivers.