A case-control study at both village and farm levels was designed to investigate risk factors for highly pathogenic avian influenza H5N1 during the 2007 outbreaks in one province of Northern Vietnam. Data related to human and natural environments, and poultry production systems were collected for 19 case and 38 unmatched control villages and 19 pairs of matched farms. Our results confirmed the role of poultry movements and trading activities. In particular, our models found that higher number of broiler flocks in the village increased the risk (OR = 1.49, 95% CI: 1.12-1.96), as well as the village having at least one poultry trader (OR = 11.53, 95% CI: 1.34-98.86). To a lesser extent, in one of our two models, we also identified that increased density of ponds and streams, commonly used for waterfowl production, and greater number of duck flocks in the village also increased the risk. The higher percentage of households keeping poultry, as an indicator of households keeping backyard poultry in our study population, was a protective factor (OR = 0.95, 95% CI: 0.91-0.98). At the farm level, three risk factors at the 5% level of type I error were identified by univariate analysis: a greater total number of birds (P = 0.006), increase in the number of flocks having access to water (P = 0.027) and a greater number of broiler flocks in the farm (P = 0.049). Effect of vaccination implementation (date and doses) was difficult to investigate because of a poor recording system. Some protective or risk factors with limited effect may not have been identified owing to our limited sample size. Nevertheless, our results provide a better understanding of local transmission mechanisms of HPAI H5N1 in one province of the Red River Delta region in Vietnam and highlight the need to reduce at-risk trading and production practices.