Background: Hurricanes often flood homes, sewers, and drinking water systems, which can spread pathogens. Contact with pathogen-contaminated water can result in diarrhea, vomiting, nausea, or other gastrointestinal distress, known collectively as acute gastrointestinal illness (AGI). Hurricane Florence was a Category 4 hurricane that hit North Carolina (NC) in September 2018, causing extensive flooding. We investigated hurricane flooding in relation to AGI to inform future disaster planning. Methods: We obtained flood inundation data from the NC Department of Public Safety and calculated the percent of area flooded in each NC zip code after Hurricane Florence (among flooded zip codes: mean=16%, range=0.0006-100%). Zip codes that flooded ≥30% (N=104) were compared to those with no flooding. We used NC’s syndromic surveillance system to calculate rates of AGI emergency department (ED) visits. We calculated rate ratios by comparing the AGI rates in flooded areas during the 3 weeks after Florence’s landfall to the rates in these same zip codes during the 3 weeks before Florence. We compared these to the rate ratio in unflooded areas. We stratified by age and race to identify demographic patterns. Results: We observed a 19% increase in AGI ED visits in zip codes with ≥30% flooding during the 3 weeks after Florence compared to the 3 weeks before Florence (RR=1.19, 95% CI: 1.04, 1.36). During this same period, AGI rates in zip codes without flooding increased only 3% (RR=1.03, 95% CI: 0.99, 1.08). In areas that flooded ≥30%, the increase in AGI rate was highest for children ages 5-17 (RR=2.00, 1.09, 3.82) and American Indians (RR=1.92, 95% CI: 1.20, 3.16). Conclusions: Hurricane Florence flooding was associated with an increase in AGI rates, especially among American Indians, who have often been pushed to less desirable, flood-prone land, and NC children.