A retrospective descriptive epidemiological study of an incidence rate and prophylaxis of tick-borne encephalitis (TBE) was carried out in the Republic of Khakassia over 2007–2016. Also, a relative risk (RR) of the incidence rate was assessed in the cohorts of vaccinated and unvaccinated population. Over the decade, 569 TBE cases were registered. There is a distinct tendency of TBE rate reduction (slope coefficient of the regression line b = –1.1 per annum, P < 0.05) as well as an expressed irregularity in the territorial distribution of longterm average annual rates in various towns and rural districts (from 0.9 up to 44.2 cases per 100 thousand people). In the vaccinated population cohort the TBE was registered 22.8 times less than in the unvaccinated one: χ2 = 23.78 (P < 0.001); RR = 3.1 (1.9–4.9). As the extend of mass-vaccination (b = 0.06 per annum, P < 0.05) and the area of acaricide treatments (b = 0.09 per annum, P < 0.05) were increasing, the number of virus-carrying ticks was reducing (b = –0.09 per annum, P < 0.001). The results of the comparison analysis of affect to the incidence of TBEcontrollable and uncontrollable factors in the territories with various rates of incidence prove the practicability of a risk-based approach to the prophylaxis of tick-borne encephalitis.