The epidemic of the 2016–2017 influenza season in Taiwan started early with moderate activity and was predominated by the influenza A(H3N2) virus. However, the influenza activity increased dramatically during the late stage of the 2016–2017 season.The genetic and antigenic characteristics of the influenza A(H3N2) virus circulating in Taiwan during the 2016–2017 season were investigated. The relationship between virus clades and the patients’ 2016–2017 vaccination histories was determined.Respiratory samples from patients with influenza-like illness in the community, clustered outbreaks, and inpatients with severe complications were tested for influenza virus. Influenza gene sequencing, phylogenetic analysis and hemagglutination inhibition assay were performed.A total of 1185, 690 and 353 cases of outpatients, inpatients and cluster events were tested positive for the A(H3N2) virus in this report. Multiple clades of the H3N2 virus co-circulated. New genetic variants were detected, including clade 3C.2a.1 with additional N121 K, K92R or T135 K mutations, 3C.2a.3a with T135 K and R150 K mutations and 3C.2a.4. The proportions of N121 K and T135 K mutations were continuously increasing. Most of the viruses (85.4%, 111/130) were antigenically related to the current vaccine strain. Infection by different clade H3N2 viruses did not correlate with immunization with the 2016–2017 vaccine.The data in this study indicate that antigenic drift is not the primary determinant of the epidemic wave at the end of the 2016–2017 season. The fitness changes in new variants, waning immunity and climatic changes are considered as possible contributors to the resurgence of the influenza A(H3N2) virus.