Hydrologic conditions are critical to the nesting behavior and reproductive success of crocodilians. In South Florida, USA, growing human settlement has led to extensive surface water management and modification of historical water flows in the wetlands, which have affected regional nesting of the American alligator (Alligator mississippiensis). Although both natural and anthropogenic factors are considered to determine hydrologic conditions, the aspects of hydrological patterns that affect alligator nest effort, flooding (partial and complete), and failure (no hatchling) are unclear. We deconstructed annual hydrological patterns using harmonic models that estimated hydrological matrices including mean, amplitude, timing of peak, and periodicity of surface water depth and discharge and examined their effects on alligator nesting using survey data from Shark Slough, Everglades National Park, from 1985 to 2005. Nest effort increased in years with higher mean and lesser periodicity of water depth. A greater proportion of nests were flooded and failed when peak discharge occurred earlier in the year. Also, nest flooding rates were greater in years with greater periodicity of water depth, and nest failure rate was greater when mean discharge was higher. This study guides future water management decisions to mitigate negative impacts on reproduction of alligators and provides wildlife managers with a tool for assessing and modifying annual water management plans to conserve crocodilians and other wetland species.