Florida's Big Bend region hosts the second largest concentration of breeding American Oystercatchers in the state, but reproductive success is low. Nest site characteristics and predation were examined to determine their influence on survival of nests and broods at two areas in the southern Big Bend (Cedar Key and Barge Canal). The probability of a nest surviving in Cedar Key was low (x̄ = 0.25, CI = 0.13–0.41) and limited by nest overwash (46% of known nest attempts); survival of nests at Barge Canal was much higher (x̄ = 0.45, CI = 0.31–0.58). However, 40% of chicks that survived to fledge (35 days) at Barge Canal died before reaching independence (60 days). Raccoon presence and hatch date were negatively correlated with brood survival at Barge Canal. Finally, chicks at Barge Canal weighed less and were smaller compared to chicks at an Atlantic Coast site, which may be related to low abundance of live oysters within 100 m of their nest sites. Efforts to enhance oystercatcher reproductive success may require different approaches for each site: habitat restoration to increase elevation of nest sites in Cedar Key and reduction of predators at Barge Canal.