In this article we describe the process of an interdisciplinary case study that examined the social contexts of occupational and general health disparities among health care workers in two sets of New England hospitals and nursing homes. A political economy of the work environment framework guided the study, which incorporated dimensions related to market dynamics, technology, and political and economic power. The purpose of this article is to relate the challenges encountered in occupational health care settings and how these could have impacted the study results. An innovative data collection matrix that guided small-group analysis provided a firm foundation from which to make design modifications to address these challenges. Implications for policy and research include the use of a political and economic framework from which to frame future studies, and the need to maintain rigor while allowing flexibility in design to adapt to challenges in the field.