This study aimed to investigate the prevalence of influenza A viruses in birds and humans residing in the same localities of Sharkia Province, Egypt and the risk factors´ assessment in poultry farms. A total of 100 birds comprised of 50 chickens, 25 ducks and 25 wild egrets were sampled. Swab samples were collected from 65 people (50 poultry farm workers and 15 hospitalized patients). All samples were screened for the presence of influenza A viruses using isolation and molecular assays. Avian influenza viruses were only detected in chicken samples (18%) and molecularly confirmed as subtype H5. The infection rate was higher in broilers (40%) than layers (8.6%). Influenza A (H1) pdm09 virus was detected in a single human case (1.54%). All the isolated AI H5 viruses were clustered into clade (2.2.1.2) and shared a high similarity rate at nucleotides and amino acid levels. In addition, they had a multi-basic amino acid motif (???PQGEKRRKKR/GLF???) at the H5 gene cleavage site that exhibited point mutations. Chicken breed, movement of workers from one flock to another, lack of utensils´ disinfection and the introduction of new birds to the farm were significant risk factors associated with highly pathogenic AI H5 virus infection in poultry farms (p?≤?0.05). Other factors showed no significant association. The HPAI H5 viruses are still endemic in Egypt with continuous mutation. Co-circulation of these viruses in birds and pdm09 viruses in humans raises alarm for the emergence of reassortant viruses that are capable of potentiating pandemics.