In Japan, the society has undergone rapid aging and falling birthrates, and issues for solving problems of health and improving quality of life have become diversified and complicated. For realizing sustainability of regional development, the issues of innovative creation has become urgent along with the progress of globalization and tightening constraints on the environment and resources. This study aimed to build a theoretical model for regional innovation based on the strategy of collaborative advantage and empirically clarify the policy issues for regional innovation focusing on the “health-related industry cluster” in Niigata Prefecture, Japan. More specifically, we clarified the situation of the “health-related industry cluster” and impacts of spatiality on knowledge flow in the regional innovation system based on interview surveys of intermediate organizations and questionnaires targeting the members of the cluster. Additionally, we identified the relationships between cognitive distance of inter-firms and innovation creation based on the analysis of annual security reports of three leading companies in the cluster using the TF-IDF (Term Frequency-Inverted Document Frequency) method. Finally, we draw policy implications for strategies of regional innovation based on the analytical results. JEL Classification:O30, R58