The seismic events that have affected the building heritage over the past years have highlighted the vulnerability and the huge direct and indirect losses associated with earthquakes. The research of methodologies able to evaluate the post-earthquake damage state is clearly decisive to allow a quick and safe estimation of the building state in the immediate hours following the event, reducing in this way the interruption of serviceability. The aim of this article is to compare the suitability of different damage indexes developed in the literature over the years. The efficiency of each index, in terms of precision of damage evaluation for structural and non-structural elements, has been tested by applying them to synthetic outputs extracted from a bidimensional RC-frame modeled with OpenSees. In particular, the response of the RC-frame has been studied using a database made of 48 real seismic accelerations classified by soil site conditions, magnitude and distance from epicenter. It is worth noting that the implementation regard both indexes related to local damage both indicators that express global damage simply through a number. In the last section, the most capable indexes have been analyzed starting from the parameters involved in their mathematical formulation in order to outline which ones are compatible with a real-time evaluation registered by a minimal equipment installed on the building (i.e. accelerometers), making them fully operational in estimating post-earthquake damage.