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Thailand has recently had 3 epidemic waves of highly pathogenic avian influenza (HPAI); virus was again detected in July 2005. Risk factors need to be identified to better understand disease ecology and assist HPAI surveillance and detection. This study analyzed the spatial distribution of HPAI outbreaks in relation to poultry, land use, and other anthropogenic variables from the start of the second epidemic wave (July 2004–May 2005). Results demonstrate a strong association between H5N1 virus in Thailand and abundance of free-grazing ducks and, to a lesser extent, native chickens, cocks, wetlands, and humans. Wetlands used for double-crop rice production, where free-grazing duck feed year round in rice paddies, appear to be a critical factor in HPAI persistence and spread. This finding could be important for other duck-producing regions in eastern and southeastern Asian countries affected by HPAI.