This paper presents first results of a research focused on the effects of piles layout and inclination on the nonlinear seismic response of bridge piers. In particular, some case studies are analysed highlighting some interesting aspects of the research. The analysis methodology, based on the substructure approach, is firstly presented. The soil-foundation system is studied in the frequency domain according to a numerical model developed by the authors that allows computing the frequency dependent impedances of the soil-foundation system as well as the foundation input motion. The inertial interaction analysis of the superstructures are performed in the time domain to capture the non-linear structural behaviour and a suitable lumped paramet...