Purpose: To assess the validity of the Physical and Mental Component Summary scores (PCS and MCS) of the 12-item Short-Form Health Survey (SF-12), a measure of health-related quality of life (HRQoL), among persons with a history of stroke. Methods: Persons with (n = 2,581) and without (n = 38,066) a reported history of stroke were enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Confirmatory factor analysis methods were used to evaluate the fit of a 2-factor model that underlies the PCS and MCS and to examine the equivalence of the factors across both study groups. Results: The 2-factor model provided good fit to the data among individuals with and those without a self-reported history of stroke. Item factor loadings were found to be largely invariant across both groups, and correlational analyses confirmed that the two latent factors were highly related to the PCS and MCS scores, calculated by the standard scoring algorithms. The effect of stroke history on physical health was more than twice its effect on mental health. Conclusions: The psychometric measurement model that underlies the PCS and MCS summary scores is comparable between persons with and without a history of stroke. This suggests that the SF-12 has adequate validity for measuring HRQoL not only in the general population but also in cohorts following stroke. © 2010 Springer Science+Business Media B.V.