Background and Aim: Acute hepatopancreatic necrosis disease (AHPND) is a severe disease in shrimp farms and adversely affected the shrimp industry of Vietnam. So far, the study on risk factors associated with AHPND outbreaks is limited. The objective of this study was to determine the potential risk factors of AHPND at the shrimp farm level in Bac Lieu Province, Vietnam. Materials and Methods: Real-time-Polymerase chain reaction was used to analyze data collected from an active surveillance program of shrimp farms in 2017 in the Vinh Tien and Vinh Lac villages, Vinh Thinh commune, Hoa Binh district in Bac Lieu Province, Vietnam. The matched case-control study selected 20 cases and 20 control farms from 134 shrimp farms. In 2018, face-to-face interviews using structured questionnaires were conducted with the farmers of these selected farms. Results: Of the 59 studied variables, seven had p≤0.2 based on bivariate analyses. The results of multivariable analysis showed that the presence of fish-eating birds on shrimp farms was a significant association with AHPND (odds ratio=8, p=0.049). Conclusion: To reduce the effect of AHPND, farmers should apply effective methods to manage wild animals such as using a grid or net to cover the pond, combined with improved biosecurity.