An evaluation is presented of the response of a 3-storey R/C structure during the destructive Lefkada earthquake of 14/08/2003. Key aspects of the event include: (1) the unusually strong levels of ground motion (PGA = 0.48 g, $SA_{max}$ = 2.2 g) recorded approximately 10 km from fault, in downtown Lefkada; (2) the surprisingly low structural damage in the area; (3) the very soft soil conditions ($V_{s,max}$ = 150 m/s). Structural, geotechnical and seismological aspects of the earthquake are discussed. The study focuses on a 3-storey building, an elongated structure of rectangular plan supported on strip footings, that suffered severe column damage in the longitudinal direction, yet minor damage in the transverse one. Detailed spectral and time-history analyses highlight the interplay of soil, foundation and superstructure in modifying seismic demand in the two orthogonal directions of the building. It is shown that soil-structure interaction may affect inelastic seismic response and alter the dynamic behavior even for relatively flexible systems such as the structure at hand.