Introduction. The problem of premature mortality from drug poisoning continues to remain relevant for many regions of the Russian Federation. The high degree of relevance is primarily due to significant losses of society in the demographic sphere, and as a result, the high level of economic losses caused by this phenomenon. Purpose: To assess the economic losses from premature mortality due to drug poisoning in the Samara region in 2017-2021, based on the determination of the number of potential years of lost life (PYLL). Materials and methods. Using the data of the Regional Register of Mortality, based on information on life expectancy in various groups of the region's population, the authors estimated the PYLL indicator both in the Samara region as a whole and among the urban and rural population. Further, based on the data obtained, the economic damage from premature mortality was estimated to. Results. The number of PYLL from drug poisoning in the Samara region from 2017 to 2021 amounted to 16417.9 years. The PYLL was calculated among men, women, as well as among the urban and rural population. The average age of the dead was 35,3±0,5 years. The age of the deceased in rural areas was statistically significantly lower than in the cities of the region, which increases the PYLL rate in the countryside. The total economic damage from drug poisoning in the region amounted to 15566.8 million rubles. Conclusion. The results of the assessment of economic damage indicate that annual losses due to premature mortality from drug poisoning in the Samara region range from 2.0 to 4.5 billion rubles. The increase in damage is facilitated by a decrease in the average age of death from poisoning, which leads to an increase in the number of potential years of life lost.