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The Yamal Peninsula in the Russian Federation experienced a massive outbreak of anthrax in reindeer (Rangifer tarandus) in July–August 2016, with 2,650 (6.46% of the total susceptible population) animals infected, of which 2,350 died (case fatality rate of 88.67%). In our study, we analyzed climatic and epidemiological factors that could have triggered the outbreak. The cancelation of reindeer vaccination against anthrax in 2007 resulted in an increase in population susceptibility. In response to the outbreak, total vaccination of all susceptible animals was resumed. To assess the vaccination effectiveness, we tested 913 samples of blood serum taken from vaccinated reindeer using an antigenic erythrocyte diagnostic kit to detect specific anti-anthrax antibodies via an indirect hemagglutination assay (IHA) 9 months after vaccination. We found that 814 samples had sufficiently high levels of anti-anthrax antibodies to indicate a protection level of 89% (95% confidence interval: 87–91%) of the whole reindeer population. Abnormally high ambient temperature in the summer of 2016 contributed to the thawing of permafrost and viable Bacillus anthracis spores could have become exposed to the surface; the monthly average air temperatures in June, July, and August 2016 were 20–100% higher than those of the previous 30-year period, while the maximum air temperatures were 16–75% higher. Using the projected climate data for 2081–2100 according to the “worst case” RCP8.5 scenario, we demonstrated that the yearly air temperature may average above 0°C across the entire Yamal Peninsula, while the yearly number of days with a mean temperature above 0°C may rise by 49 ± 6 days, which would provide conditions for reactivation of soil anthrax reservoirs. Our results showed that the outbreak of anthrax occurred under conditions of a significant increase in air temperature in the study area, underlined the importance of vaccination for controlling the epidemic process, and demonstrated the effectiveness of monitoring studies using the IHA diagnostic kit for detecting erythrocyte anthrax antigens.