OBJECTIVE: To examine the relationship between flood severity and risk of hospitalisation in the Vietnam Mekong River Delta (MRD). METHODS: We obtained data on hospitalisations and hydro-meteorological factors during 2011-2014 for seven MRD provinces. We classified each day into a flood-season exposure period: the 2011 extreme annual flood (EAF); 2012-2014 routine annual floods (RAF); dry season and non-flood wet season (reference period). We used province-specific Poisson regression models to calculate hospitalisation incidence rate ratios (IRRs). We pooled IRRs across provinces using random-effects meta-analysis. RESULTS: During the EAF, non-external cause hospitalisations increased 7.2% (95% CI 3.2% to 11.4%); infectious disease hospitalisations increased 16.4% (4.3% to 29.8%) and respiratory disease hospitalisations increased 25.5% (15.5% to 36.4%). During the RAF, respiratory disease hospitalisations increased 8.2% (3.2% to 13.5%). During the dry season, hospitalisations decreased for non-external causes and for each specific cause except injuries. CONCLUSIONS: We observed a gradient of decreasing risk of hospitalisation from EAF to RAF/non-flood wet season to dry season. Adaptation measures should be strengthened to prepare for the increased probability of more frequent extreme floods in the future, driven by climate change.