There is considerable global concern over the newly emergent H5N1 strain of avian influenza that had affected millions of domestic poultry flocks and resulted in 256 human cases and 152 deaths in humans. There has been little analysis of the general assumption that smallholder backyard poultry flocks are inherently at higher risk of highly pathogenic avian influenza (HPAI) than confined and commercial scale operations. Data from Thailand in 2004, was utilised to test the relative risks of HPAI infection in poultry flocks, by species, type of operation, and geographic location. The results indicate that backyard flocks are at significantly lower risk of HPAI infection compared to commercial scale operations of broiler or layer chickens or quail. These results are plausible in terms of the opportunities for breach of bio-security in commercial scale operations. Both experimental and observational studies in developed country settings have demonstrated the capacity of microbes to enter and leave these larger operations despite the implementation of standard bio-security measures. The results of this study should be considered by policy makers and public health officials when developing plans to control or prevent HPAI while aiming to limit adverse effects on the livelihood of smallholder poultry producers in developing countries.