This article investigates the effect of response styles (RSs) on rural–urban measurement comparability in Guyana. It uses the representative indicators response styles means and covariance structure (RIRSMACS) model and finds that traditional measurement invariance (MI) tests provide inadequate assurance of the absence of rural–urban measurement bias when RSs are not controlled. Even when MI is achieved, RSs can still differentially affect measurements and substantive results between rural and urban regions. In addition, a lack of MI may be at least partially due to RSs bias, but MI may also be due to RSs. Therefore, adjustments for RSs are necessary and researchers should be cautious about pooling data across rural and urban areas without controlling RSs.