The paper presents a study on the seismic fragility of Reinforced Concrete (RC) bridges isolated by elastomeric bearing devices subjected to differential displacements induced by slow-moving landslides. The seismic behaviour of isolated bridges is ruled by the performance of elastomeric bearings to reduce and dissipate earthquake actions. These bridges are subjected to service loads that usually are accounted for in design, but possible additional actions from the surrounding environment, such as landslides affecting substructure components, can seriously undermine the seismic response. The paper describes a practical approach to investigate the seismic fragility and risk of RC bridges isolated by elastomeric bearings, which may undergo early deformations induced by the differential displacements of substructure components. On the basis of previous existing studies, the proposed methodology is based on numerical modelling accounting for landslide-induced substructure displacements and proper modifications on the constitutive law and hysteretic response of the elastomeric bearings. Subsequently, after establishing specific limit-states, nonlinear time history analyses of the seismic response are used to estimate fragility curves and risk indicators. The study points out that it is possible to quantify the influence of landslide-induced effects on seismic fragility and risk by using only two numerical models, in order to provide decision support to transportation authority responsible for ensuring the safety of bridges and road networks. The proposed approach has been tested on a real-life case study, the Santo Stefano Viaduct in Italy, which was subjected in the past to relevant deformations of the elastomeric bearings due to an active landslide phenomenon.