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A decade long study was conducted to investigate the ecological, biological, and temporal conditions that affect concentrations of Vibrio spp. bacteria in a well-studied lagoonal estuary. Water samples collected from the Neuse River Estuary in eastern North Carolina from 2004-2014 (with additional follow-up samples from Fall of 2018) were analyzed to determine Vibrio spp. concentrations, as well as the concentrations of inorganic and organic nutrients, fecal indicator bacteria, phytoplankton biomass, and a wide range of other physiochemical estuarine parameters. A significant increase in Vibrio spp. was observed to occur in the estuary over the examined period. Strikingly, over this long duration study period, this statistically significant increase in total culturable Vibrio spp. concentrations does not appear to be correlated with changes in salinity, temperature, or dissolved oxygen, the three most commonly cited influential factors that predict estuarine Vibrio spp. abundance. Furthermore, shorter term (similar to 3 years) data on specific Vibrio species (V. vulnificus and V. parahaemolyticus) show that while Vibrio spp. are increasing overall as a genus, the numbers of some key potentially pathogenic species are decreasing as a part of the total population, further supporting the concept that quantification of the entire genus is not a worthwhile use of resources toward predicting levels of specific potentially pathogenic species of public health concern. The significant increase in this concentration of Vibrio spp. in the studied estuary appears to be related to nitrogen and carbon in the system, indicating a continued need for further research.