The impact of annual influenza epidemics and prevailing strains varies worldwide and regional. The majority of vaccines used contained two influenza A strains and only one influenza B strain (trivalent vaccine). The aim of the study was to compare laboratory confirmed influenza B cases during three consecutive years with respect to vaccination history, clinical symptoms and molecular virology. Partial HA gene sequences were analyzed for lineage determination and complete HA sequence in cases with reported vaccination and in fatal cases. Clinical data were retrieved from patient charts. During the 2015/16 season, 75 influenza B cases were retrieved; 11 in 2016/17, and 274 in 2017/18. The frequency of Yamagata-lineage strains increased from 7.6% to 100%. No difference was detected in the relative frequency of co-morbidities in season 2017/18. 37.7% of the adult patients and 4.5% of pediatric patients were vaccinated against influenza. Phylogenetically, Yamagata strains clustered similarly in 2017/2018 when compared to the previous two influenza seasons. While the relative frequency of influenza B cases differed, the clinical symptoms remained similar. World Health Organization recommendations for the use of tetravalent vaccines that contain two influenza B strains (Yamagata and Victoria) in addition to the two influenza A strains (H1N1 and H3N2) should be implemented in national vaccination guidelines. This research was partially supported by the Association of Sponsors and Friends of Leipzig University. [ABSTRACT FROM AUTHOR]