Background: Organizations in the pharmaceutical industry are highly dependent on the institutional environment. The introduction of pharmacoeconomics to the decision-making on the price and reimbursement decisions became strong constraints to pharmaceutical companies in Korea. As little is known about the issue on organization-environment interaction in the healthcare field, this study aimed to figure out how pharmaceutical companies adapted to the environmental changes. Methods: A multicase study method was used, selecting eight cases among multi-national pharmaceutical companies in South Korea. In-depth interviews were conducted with the managers of these organizations, and secondary data were reviewed to complement the interviews. Results: Pharmaceutical companies viewed the new policies as a big threat and sought for actions against them. One of the most distinguishing organizational changes was to construct a Market Access department. Other strategies managing the environment such as co-optation, forecasting, and bargaining were also implemented. These changes were consistent with the predictions of Resource Dependency Theory and Institutional Theory. Conclusions: The interactions between pharmaceutical companies and institutional environments in healthcare were first explored. This study presents a new perspective on how organizations change and the motives for the changes. The findings of this case study will form the basis of further empirical studies.