Florida is a hotspot for nonindigenous fishes with over 30 species established, although few of these are small-bodied species. One hypothesis for this pattern is that biotic resistance of native species is reducing the success of small-bodied, introduced fishes. The eastern mosquitofish Gambusia holbrooki is common in many freshwater habitats in Florida and although small-bodied (<50 mm), it is a predator and aggressive competitor. We conducted four mesocosm experiments to examine the potential for biotic resistance by eastern mosquitofish to two small-bodied nonindigenous fishes, variable platyfish (Xiphophorus variatus) and swordtail (X. hellerii). Experiments tested: (1) effect of eastern mosquitofish density on adult survival, (2) effect of eastern mosquitofish on a stage-structured population, (3) role of habitat structural complexity on nonindigenous adult survival, and (4) behavioral effects of eastern mosquitofish presence and habitat complexity. Eastern mosquitofish attacked and killed non-native poeciliids with especially strong effects on juveniles of both species. Higher eastern mosquitofish density resulted in greater effects. Predation on swordtails increased with increasing habitat complexity. Eastern mosquitofish also actively drove swordtails from cover, which could expose non-native fish to other predators under field conditions. Our results suggest that eastern mosquitofish may limit invasion success.