The problem of a comprehensive assessment of the effectiveness of enterprises innovative activities is considered. It was found that traditional approaches and methods of a comprehensive (system) assessment of the enterprises (project) efficiency do not provide simultaneous using of different indicators like social, economic and environmental effectiveness and cannot be used to evaluate an projects efficiency with a social orientation, and do not compare projects from a position their competitiveness and environmental friendliness. The multidimensional criterion has been developed for a comprehensive assessment of innovative projects efficiency, providing a justification for the quality of the project and its quantitative assessment, taking into account the social, economic and environmental components of its efficiency. A conceptual scheme of the approach to assess­ing innovation projects efficiency on the basis of the principle of non-linear synthesis of indicators, which reflects the multi-step process for its identification, has been proposed. This scheme was not previously presented in existing methods for innovative projects efficiency evaluation. The system-dynamic model for a comprehensive assessment of an innovative project efficiency for the production of raw materials for an antiarrhythmic drug is proposed. This model allows to draw the situational analysis of the factors changes impact into the project efficiency. The model differs from the existing ones in that it takes into account the multiplicative influence of the factors that allows project manager to reproduce the systemic (synergetic) effect of the project. Experimental studies of the proposed approach on the actual data of a specific project were carried out and the reliability of the proposed theoretical principles and the developed method of a comprehensive assessment of innovative project efficiency were proved. The testing results of the proposed theoretical principles and approach have practical significance.