This study investigated the pathogenicity and transmissibility of a reverse-genetics-derived highly pathogenic avian influenza (HPAI) H5N1 lineage influenza A virus that was isolated from a human, A/Iraq/755/06. We also examined surface gene reassortant viruses composed of the haemagglutinin and neuraminidase from A/Iraq/755/06 and the internal genes of a 2009 pandemic H1N1 virus, A/New York/18/2009 (2Iraq/06 : 6NY/09 H5N1), and haemagglutinin and neuraminidase from A/New York/18/2009 with the internal genes of A/Iraq/755/06 (2NY/09 : 6Iraq/06 H1N1). The parental A/Iraq/755/06 caused little to no lesions in swine, limited virus replication was observed in the upper respiratory and lower respiratory tracts and transmission was detected in 3/5 direct-contact pigs based on seroconversion, detection of viral RNA or virus isolation. In contrast, the 2Iraq/06 : 6NY/09 H5N1 reassortant caused mild lung lesions, demonstrated sustained virus replication in the upper and lower respiratory tracts and transmitted to all contacts (5/5). The 2NY/09 : 6Iraq/06 H1N1 reassortant also caused mild lung lesions, there was evidence of virus replication in the upper respiratory and lower respiratory tracts and transmission was detected in all contacts (5/5). These studies indicate that an HPAI-derived H5N1 reassortant with pandemic internal genes may be more successful in sustaining infection in swine and that HPAI-derived internal genes were marginally compatible with pandemic 2009 H1N1 surface genes. Comprehensive surveillance in swine is critical to identify a possible emerging HPAI reassortant in all regions with HPAI in wild birds and poultry and H1N1pdm09 in pigs or other susceptible hosts.