In this paper probabilistic seismic loss assessment of RC high rise-buildings for seismic excitation typical for Southern Euro-Mediterranean zone is presented. The loss assessment methodology developed in paper is based on a comprehensive simulation approach which takes into account ground motion (GM) uncertainty, the random effects in seismic demand as well as in predicting the damage states (DSs). The methodology is implemented on three RC high-rise buildings of 20-story, 30-story and 40-story with core wall structural system designed according to Eurocode 8. The loss functions described by a cumulative lognormal probability distribution are obtained for two intensity level for a large set of simulations (non-linear time-history analyses) based on 60 GM records with wide range of magnitudes, distance to source and different site soil conditions. The losses expressed in percent of building replacement cost for RC high-rise buildings are obtained. In the estimation of losses, both structural (S) and non-structural (NS) damage for four DSs are considered. The effect of different GM characteristics (magnitude, distance to source and site soil condition) on the obtained losses are investigated. It is checked if the estimated performance of the RC high-rise buildings fulfill limit state requirements according to Eurocode 8.