Objective : To study the regional features of the West Nile fever (WNF) epidemic process manifestations using the example of the territory with stable and long-term pathogen circulation (Volgograd Oblast). Materials and Methods : We used the data of the Reference Center for monitoring the WNF pathogen based on the Volgograd Research Anti-Plague Institute of Rospotrebnadzor over 1999–2021. The main method is a comprehensive epidemiological method. Results : The long-term changes in the WNF incidence in Volgograd Oblast is characterized by a cyclical nature with an interval of 1–8 years and a tendency to decrease. The maximum risk of infection occurs in August (58.8%), but there is an increase in the number of cases in September. The average duration of the epidemic season is 8.4 weeks. Case fatality rate is at the level of 4.3%; the prevalence of the number of deaths in the group of 70 years and older (75%), as well as among men (63.6%) has been established. The greatest contribution to the incidence rate is made by the age group of 60 years and older (37.7%). Features of the clinical presentation include the dominance of forms without damage to the central nervous system (91.1%) and moderate clinical course (72.3%). The prevalence of the urban population among the infected was noted (85.5%). Conclusion : A comparative analysis of the clinical and epidemiological WNF manifestations in Volgograd Oblast, territories with a stable circulation of the pathogen (Astrakhan and Rostov Oblasts) and, in overall, the Russian Federation, established differences in the duration of cyclical fluctuations in incidence, seasonality (Rostov Oblast), age structure of incidence (Astrakhan Oblast), distribution of cases by the severity of the clinical course, the site of the alleged infection and social status.