Our research aim was to estimate efficiency of emergency disinsection and deratization that were accomplished to reduce risks of diseases among population in Gorno-Altaiskiy high-mountain natural plague focus. The research was performed in 2016–2021 in Gorno-Altaiskiy high-mountain plague focus which is the northern part of Sailygem cross-border natural focus located both in Russia and Mongolia. Zoological, epizootologic, epidemiological and statistical research procedures as well as GIS-tools were applied to collect and analyze research data. Epidemiologic surveillance over plague in the focus has been accomplished since 1961. Prior to 2011 only rhamnoso-positive strains of the plague microbe with selective virulence were found here, belonging to the Central Asian subspecies Yersinia pestis altaica, circulating mainly in the population of the Ochotona pallassi. Given that, the focus was believed to have low epidemic potential. Since 2012 highly virulent strains of the basic plague microbe Yersinia pestis ssp. pestis started to occur in populations of Marmota baibacina and other carriers. As a result, starting from that period of time, epidemiologic status of the focus changed and it led to 3 cases of bubonic plague among humans in 2014–2016. Disinsection and deratization remained the major components in anti-epidemic activities aimed at non-specific plague prevention. In 2016–2021 fields disinsection covered a total square equal to 162.7 km2; disinsection in settlements, 127.3 thousand m2; deratization in settlements, 461.7 thousand m2. An approach involving disinsection only on land spots that were considered epidemically hazardous was first implemented; such land spots were around livestock breeders’ camps located within boundaries of detected epizooties. Efficiency of fields disinsection amounted to 94.6; disinsection in settlements, 100 %; deratization in settlements, 88.0 %. Population of plague vectors and carriers was controlled bearing in mind environmental aspects in regulating numbers of animals and compliance with environmental protection requirements. Deratization and disinsection, together with other activities aimed at plague prevention, provide epidemiologic welfare in the focus and reduce its epizootic activity.