In Japan, outbreaks of H5N8 highly pathogenic avian influenza (HPAI) were reported between November 2020 and March 2021 in 52 poultry farms. Understanding HPAI epidemiology would help poultry industries improve their awareness of the disease and enhance the immediate implementation of biosecurity measures. This study was a simulation-based matched case-control study to elucidate the risk factors associated with HPAI outbreaks in chicken farms in Japan. Data were collected from 42 HPAI-affected farms and 463 control farms that were within a 5-km radius of each case farm but remained uninfected. When infected farms were detected as clusters, one farm was randomly selected from each cluster, considering the possibility that the cluster was formed by farm-to-farm transmission within an epidemic area. For each case farm, up to three control farms were selected within a 5-km radius. Overall, 26 case farms (16 layer and 10 broiler farms) and 75 control farms (45 layer and 30 broiler farms) were resampled 1000 times for the conditional logistic regression model with explanatory variables comprising geographical factors and farm flock size. A larger flock size and shorter distance to water bodies from the farm were found to increase infection risk in layer farms. Similarly, in broiler farms, a shorter distance to water bodies increased infection risk. On larger farms, frequent access of farm staff and instrument carriages to premises could lead to increased infection risk. Waterfowl visiting water bodies around farms may also be associated with infection risk.Copyright © 2023. Published by Elsevier Ltd.