The peculiarities of the course of the epidemic process of HIV infection, including the formation of certain risk groups by gender, age and social status, are relevant, as they allow the development of specific preventive measures. The aim is to identify risk groups for HIV infection among the population of the Omsk region in 1996–2023. Data from the main statistical reporting forms, the Federal Register of Persons Infected with the Human Immunodeficiency Virus, and the results of epidemiological investigations were used for the analysis. The analysis made it possible to establish the main trends in the development of the epidemic process of HIV infection in the Omsk region. The general trend of decreasing morbidity has been revealed, which coincides with that in the Russian Federation, primarily due to the large volume of preventive measures carried out. Changes in the characteristics of the risk groups of infection have been established — the contingents of injecting drug users and men who have sex with men, prevailing at an early stage of the epidemic, have been replaced by persons who became sexually infected from individuals of the opposite sex. At the same time, the proportion of infected women approached that of men. This entailed the risk of perinatal transmission of HIV infection. The introduction of mandatory screening for HIV infection markers in pregnant women and the implementation of antiretroviral prophylaxis has reduced the number of cases of perinatal infection of newborns to a minimum. An increase in the share of the rural population in the total structure of newly diagnosed people with HIV infection may indicate both lower awareness of this problem and shortcomings in the provision of medical care, its lower accessibility compared to the urban population. The prevalence in the structure of HIV-infected people who are not engaged in work indicates that the most socially unprotected contingents are involved in the epidemic process, as a rule, they are not ready to take care of their own health and the health of others, often leading an antisocial lifestyle. Thus, HIV infection in the Omsk region remains one of the priority epidemiological problems requiring the formation of an integrated approach to its solution. The conducted research made it possible to identify the main risk groups for HIV infection, in relation to which targeted preventive strategies should be applied.