In the recent years, rice farmers in the Mekong River Delta (MRD) have faced increased risks of weather and pestilence, both of which directly impact the sustainability of their livelihoods. In this regard, the objective of this paper is to investigate the risk facing rice farmers and the impact of risk mitigation strategies on profit of the farmers in the Mekong Delta. The results, estimated from a sample of 342 farmers, show that 80 percent of the farmers faced two types of risk, namely weather risk, risk of crop pests and diseases. Mitigation strategies of the farmers are (1) adjusting planting schedules and growing techniques, (2) water resource management, (3) rice protection products, and (4) reducing production scale. The results of regression analysis showed that the first and second strategy are found to be positively correlated with farmer's profit. It is also revealed that farmers who actively respond to risks have higher profit than passive farmers, consistent with a common perception of "prevention is better than cure". The policy implication to be drawn from the study for the government and the MRD agricultural sector is to guide farmers in risk identification and prevention. At the same time, it is necessary to invest in upgrading the risk forecasting system in agriculture and to invest in completing irrigation infrastructure allowing actively regulate water for production.