It is the 2^nd largest basin in the territory of Vietnam, but the Red River Basin system has the highest potential of energy all over the country. In the course of “industrialisation and modernisation” of the country, a series of large hydroelectric projects have been built and put into operation; in which, the Red River Basin occupies for 25% of the construction works (as for large hydropower plants in Vietnam), but its total installed capacity accounts for more than 46%. However, during operation, the reservoirs have affected strongly the flow regime of downstream, causing disputes among water users and simultaneously increasing some types of natural disasters, including drought. To have scientific basis for assessing the impact of the regulation of the large upstream reservoirs on the flow regime and the ability to get water in the Red River downstream in the dry season, the authors have applied MIKE DHI model to simulate the flow and operation of the reservoirs during the period of 2000-2012. The results have shown that the water resources conditions and reservoir system currently can meet the present demand of the Red River downstream in the dry season. There fore, it is necessary to develop a complete inter-reservoir operation rule for the reservoir system of the Red River Basin which will resolve the water use conflicts.