The seismic performance of reinforced concrete (RC) frame structures with irregularities leading to soft first floor is studied using capacity assessment procedures. The soft first story effect is investigated for the cases: (i) slab-column connections without beams at the first floor, (ii) tall first story height and (iii) pilotis type building (open ground story). The effects of the first floor irregularity on the RC frame structure performance stages at global and local level (limit states) are investigated. Assessment based on the Capacity Spectrum Method (ATC-40) and on the Coefficient Method (FEMA 356) is also examined. Results in terms of failure modes, capacity curves, interstory drifts, ductility requirements and infills behaviour are presented. From the results it can be deduced that the global capacity of the structures is decreased due to the considered first floor morphology irregularities in comparison to the capacities of the regular structure. An increase of the demands for interstory drift is observed at the first floor level due to the considered irregularities while the open ground floor structure (pilotis type) led to even higher values of interstory drift demands at the first story. In the cases of tall first story and slab-column connections without beams soft-story mechanisms have also been observed at the first floor. Rotational criteria (EC8-part3) showed that the structure with slab-column connections without beams exhibited the most critical response.