Full time series of ground acceleration are required for nonlinear time history analyses to evaluate the dynamic response of a structure under earthquake excitations. In regions with sparse ground motion data, alternative ground motion simulation techniques are used to generate acceleration time series with varying levels of accuracy. While using simulated records for engineering purposes, it is critical to investigate the efficiency of these records in predicting the real engineering demands. For this purpose, in this study nonlinear time history analyses of typical multi-story reinforced concrete frame structures are performed to compare structural responses to synthetic records with those to the real ground motions of a particular event. The 2009 L'Aquila (Italy) (Mw=6.3) earthquake is simulated using two alternative simulation methods: the Hybrid Integral-Composite method and the Stochastic Finite-fault method. Results of nonlinear time history analyses from the real and synthetic records are compared in terms of maximum displacement of each story levels. The results from this study indicate that the match between the Fourier Amplitude Spectrum of the real and synthetic record around the frequencies that correspond to the fundamental period of the structure governs the misfit between the real and synthetic nonlinear response. We also show that even for cases where nonlinear behavior is more likely, period-dependent SDOF indicators of goodness of fit between a particular real and corresponding synthetic record (such as 5% damped response spectrum) represents the difference in MDOF behavior of frame structures due these records. Finally, we suggest that for earthquake engineering purposes where the synthetics are to be used, simulation of realistic amplitudes over the entire broadband frequency range of interest is essential.