This paper presents an integrated hydrodynamic modeling and probability analysis approach to assess the long-term effects of changing river inflows on the estuarine ecosystem. The probability analysis method, which is popularly used in advanced hydrological frequency analysis of river flows and rainfalls, has been applied to analyze the effects of changing inflow on salinity and thus on oyster ecology in Apalachicola Bay. Long-term salinity data were predicted through the application of a calibrated 3D hydrodynamic model under two river inflow conditions over a 10-year period. The first flow represents the historic flow. The 2nd flow condition, called Scenario-1, represents a regulated flow scenario to account for the potential increasing upstream water demands. Two stations, Mid Bay and Dry Bar, in the bay were selected to examine the estuarine responses. Under the historic flow condition, the maximum probability salinity at Dry Bar in the rich oyster reef is near 24 ppt, within the optimal salinity range for oyster growth of 16–26 ppt (Harned et al., 1996); the maximum probability salinity at Mid Bay station is 27 ppt, beyond the optimal salinity for oyster growth in mid-bay area where there is no oyster reef around. While it is difficult to examine the difference between two scenarios by conventional time series analysis of river flows and salinity, probability analysis reasonably characterizes and quantifies the changes of river flow and salinity patterns over the 10-year period. The Scenario-1 has caused the increase of the probability in low flows. Higher probability of low flows for the regulated flow scenario shortens the period of optimal salinity in the oyster reef, and cause substantial increase of exceedance probability of higher salinity in the oyster reef to the level beyond the optimal salinity range for oyster growth. The probability analysis approach has demonstrated its advantage for the risk assessments of the long-term estuarine ecohydrological effects under various regulated inflow scenarios to support estuarine water resources managements. 2009 Elsevier Ltd. All rights reserved.