The aim of this study was to investigate the epidemiology of influenza A virus infection in Cyprus from the 2009 pandemic until 2013. Pandemic influenza A(H1N1)2009 virus infections outnumbered infections with other respiratory viruses until the end of 2009. The pandemic virus was also the prevalent influenza strain during influenza season 2010-2011; however, it was completely replaced by H3N2 subtype in the next season. During the most recent influenza season, 2012-2013, the pandemic strain was once again the only influenza A virus circulating in Cyprus. Full-length neuraminidase gene sequencing revealed mutations that had previously been identified as permissive. No significant difference in the expression of the IFN-inducible genes OAS and IFIT1 were observed. The phylogenetic analysis of the neuraminidase gene sequences revealed a picture of continuous importation of influenza strains in the island of Cyprus with local circulation playing only a minor role in determining the prevalent strain of the next influenza season.