Abstract <p>The article examines the structure and specifics of poorly studied aspects of the synergy of institutional interactions of the triple helix model, reflecting the formation of an innovative economy in Russia. The evidence base comprises regional statistics data from federal subjects. Methods of multidimensional classification, testing of statistical hypotheses, and analysis of relationships in complex systems of institutional factors are used. Significant regional differences in the formation of an innovative economy have been identified. The classic triple helix model is implemented in less than 30% of federal subjects. In most regions, the innovation sector is either dominated by industrial enterprises that interact weakly with the scientific and educational sector, or the scientific sector is poorly oriented towards applied results. The absence of institutional intermediaries prevents the model from realizing its potential. The article shows the presence of formed or emerging institutional spheres in the Russian innovative economy. The practical implementation of the triple helix model depends on “windows of opportunity,” which are determined by a combination of regional factors and institutional policies of the federal center. The results of the study are recommended to be used in the formation of regional innovation and cluster policies, as well as in strategic developments of interregional innovation cooperation.</p>