It is the purpose of this article to describe the methodological issues when designing qualitative cultural comparative studies, which may be used to address health disparities. Overall, two broad types of comparative studies were found: primary and secondary comparative studies. Methodological issues to consider when designing primary studies were reviewed. The main areas discussed in this article relate to sampling and study purpose, sample boundaries, theoretical context, concept development, analogous comparisons, and systematic comparisons. Nurses are in a prime position to pose the qualitative research questions needed to address health disparities within their clinical settings. It is suggested that awareness of the method types and issues might inspire further qualitative comparative work.