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The article presents the rationale for using the Data Envelopment Analysis method for assessing innovation sustainability at the regional level. The theoretical basis for the paper is based on results of the study of foreign experience gained and the current Russian practice on evaluation of innovative development at the federal and regional levels. Focusing on the examined approaches, the authors propose an algorithm of regional innovative resistance estimation using the method of comparative analysis of the data with set thresholds values as well as Data Envelopment Analysis method. The results of the study can be used by regional government bodies to monitor the state of the regional innovation sphere, as well as to adjust the existing instruments of the implemented innovation policy. The proposed approach to assessing the level of innovation sustainability can be transmitted to the so-called innovation ecosystems of various types (regional, local, corporate) taking into account the determination of an appropriate system of criteria and indicators, their differentiation to input and output, as well as the formation of threshold values, if necessary, to ensure that the parameters comply with the basic principles of the methods proposed for use. [ABSTRACT FROM AUTHOR]