On 14 November 2016, an outbreak of highly pathogenic avian influenza (HPA) was reported from a commercial layer farm located in Malard, Tehran Province, Iran. This study aimed to investigate the HPAI H5N8 outbreaks in Iran. The questionnaire was prepared and completed through interviews with farm owners or field observations at the time of disease onset from November 2016 to February 2017. The HPAI H5N8 infection was confirmed in 30 different locations including 10 villages (33.3%), nine-layer farms (33%), two broiler breeder farms (6.67%), one layer breeder farm (3.3%), one turkey farm (3.3%), one partridge farm (3.3%), five national parks (16.7%), and one wetland (3.3%) in 12 provinces of Iran. The cumulative incidence rates of disease in villages, layer farms, broiler breeder farms, layer breeder farms, partridge farms, and turkey farms were 0.02%, 0.87%, 0.55%, 6.25%, 7.14%, and 0.69%, respectively. The findings reflect that among the investigated variables at infected locations, new birds entering the home in villages, live bird markets, inappropriate biosecurity conditions, transporting manure during the breeding period, close proximity of a common road to infected farms, and poultry movement inside (pullet) and outside were the most frequently observed possible risk factors for these outbreaks. In conclusion, attention should be focused on the study of the dynamics and movements of domestic poultry, investigation and modification of the structure of industrial poultry farms, training for all related people, enhancement of passive surveillance, an increase in biosecurity, raising the awareness of the authorities on the importance of the infection, and provision of the required credits and facilities.