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Empirical methods applied in Regional Innovation System (RIS) research have two shortcomings. First, they usually have difficulties when it comes to explaining the interplay and relative importance of the elements of a RIS. Second, they are not capable of showing whether specific RIS can indeed be attributed to a pre-defined region. We draw on four contrasting regions in China exhibiting strong disparities with regard to innovation resources to examine how the “Analytic Hierarchy Process” (AHP), a comparative method widely used in business and management studies, can help to address these methodological shortcomings. Results show that in combination with qualitative analyses, the AHP can support empirical RIS research to decide whether or not a particular pre-defined RIS model can adequately describe empirical reality: the AHP evaluates the relative importance of both quantitative and qualitative RIS elements contributing to innovation in a pre-defined area through comparative expert assessments. Also drawing on sensitivity checks, the AHP is capable of providing a critical evaluation of the importance of both factors and spatial delimitations affecting innovation. The method thus informs theoretical development on the elements and spatial boundaries of RIS and helps empirical innovation research to apply the RIS framework in a more fruitful manner.