Within the framework of this paper, the author’s entropy method of road safety management in large-sized systems is considered. The road safety management system in the Russian Federation, the largest country in the world, was selected for this case study. The purpose of the article is to present the opportunities and methodology of the use of quantitative assessments of the orderliness of the road accident rate formation process in regional transport systems for road safety management. Orderliness, in other words, systemic anti-chaos, can be quantified using the C. Shannon informational entropy H. The article consists of the results of the issue’s state analysis; methodology of assessment of the orderliness of the road accident rate formation process based on the using of the cause-and-effect chain; entropic method of the road safety management in large-scale systems, in particular, the algorithm of management of regional road safety in Russia taking into account the level of its entropic orderliness; and examples of the quantitative evaluation of the orderliness of regional road safety provision systems in Russia. The key results of the research are spatio-temporal patterns of the change of the orderliness of the road safety provision systems in the Russian Federation in 2004–2020. Based on the results, conclusions and recommendations about the practical application of the entropic method of road safety management in large federal states with complex administrative structures were formulated. These results give an idea of the possibilities of the usage of entropic approaches in road safety management to assess the orderliness of the regional transport systems and the advantages of the entropic method over other managerial methods.