Background Drinking water in the Mekong Delta Region (MDR) is highly vulnerable to salinity intrusion and this problem is expected to increase with the projected climate change and sea level rise. Despite this, research on health effects of saline contaminated water is scarce in this region. This study examines the risk of hospital admission for hypertension in salinity-affected areas of the MDR. Methods Cases and controls were obtained from national/provincial hospital admission records for 2013. The cases were adult patients whom hypertension (ICD10-code: I10-I15) was primary diagnosis for admission. Of the 13 provinces in the MDR, we identified seven as ‘salinity exposed’ and the remaining as ‘non-exposed’ areas. A multi-level logistic regression model was used to examine the association between salinity exposure and hypertension outcome. Results Of the total 573 650 hospital admissions, 22 382 (~3.9%) were hypertensive cases. The multi-level logistic model combining both individual and ecological factors showed a 9% increase in risk (95% CI: 3–14%) of hypertension admission among individuals in exposed areas compared to those in non-exposed areas. Conclusion In order to develop and promote appropriate adaptation strategies, further research is recommended to identify the salt exposure pathways and consumption behaviours in the salinity exposed areas.