Invasive fishes, via competition and predation, may be an important factor in endangering populations of amphibians and other aquatic fauna. The mosquitofish, Gambusia affinis, commonly stocked into amphibian breeding sites for mosquito control worldwide, has recently been found in some breeding sites of the endangered fire salamander Salamandra infraimmaculata in northern Israel. A comparison of Salamandra larvae in natural pools varying in Gambusia densities suggested that Gambusia negatively affects Salamandra by causing damage to its appendages, in particular, its tailfin (as manifested in a smaller tail:body ratio). Comparison of the same pool before and after mosquitofish introduction suggested strong negative effects on larval performance and number of emerging metamorphs. To explicitly test the hypothesis that Gambusia negatively affects Salamandra larval development, growth and survival, we conducted a replicated outdoor mesocosm experiment. In this experiment, we also tested how habitat structural complexity, in the form of radiating cords simulating artificial vegetation, might mediate damage caused by Gambusia. We used a two-by-two factorial design: the presence or absence of increased structural complexity crossed with the presence or absence of mosquitofish. After a short period, mosquitofish strongly reduced larval wet weight and survival, and increased body damage in the form of a reduced larval tail:body ratio and partially missing gills and limbs. No Salamandra larvae exposed to mosquitofish survived to metamorphosis in either habitat type. We conclude that Gambusia strongly and negatively affects Salamandra larvae and that the introduction of Gambusia into sites containing Salamandra is inconsistent with the goal of preserving this endangered urodele.