Flooding causes significant public health issues. The Mekong Delta has been considered the region to be the most vulnerable to flooding in Vietnam. This study assessed the spatial vulnerability of the health impacts of flooding in the Mekong Delta region, Vietnam. This study applied a vulnerability assessment framework which was computed as the function of three dimensions: exposure, sensitivity, and adaptive capacity. The indicators for each dimension were derived from the relevant literature, consultations with experts, and data availability. An analytic hierarchy process (AHP) and a principal component analysis (PCA) were used to determine the weight of indicators. Vulnerability indexes (VIs) were then computed for each province. A total of 29 indicators (sensitivity index, 14; adaptive capacity index, 13; and exposure index, 2) were employed to evaluate the vulnerability to the health impacts of flooding at a provincial level. The results of AHP revealed that the highest VIs were found in the Dong Thap and An Giang provinces (VI, 1.948 and 1.574, respectively). VIs were distributed with higher indexes in upstream provinces close to a river than in coastal provinces. PCA generated three components from the 29 indicators, and the VIs computed from the PCA method are in substantial agreement with the AHP method (ICC = 0.71, p < 0.05). The vulnerability to the health impacts of flooding varies from province to province in the Mekong Delta region in Vietnam. Individual plans for health preparedness and adaption to flooding should be developed for each province in the Mekong Delta region.