The accurate assessment of a solar photovoltaic (PV) system depends on reliability of the software tools used for simulation. This study compares software EnergyPlus and PVGIS web application. EnergyPlus is an engineering-oriented software that enables detailed modeling of a PV system performance, considering a large number of input parameters that affect energy yield. The PVGIS web application, on other hand, offers a simplified approach, but its accuracy compared to engineering simulations is not explicitly defined. The aim of this study is to examine to what extent PVGIS can provide results comparable to those obtained using EnergyPlus simulations. For this purpose, comparative simulations were carried out for nine different locations across the Republic of Serbia. Within the PVGIS web application, simulations were performed using two meteorological datasets (SARAH3 and ERA5), which were then compared with the results obtained using the EPW weather files in EnergyPlus. The results show differences ranging from 3.23% to 9.11% between the SARAH3 and EPW datasets, and from -2.89% to 1.82% between the ERA5 and EPW datasets. Additionally, an analysis was conducted for a known location in the city center of Kragujevac, where the PV modules would remain shaded for most of the year. The EnergyPlus simulation results indicated a 63.4% lower energy yield compared to the PVGIS simulation using the SARAH3 dataset and 65.6% lower compared to the ERA5 dataset. The obtained results clearly indicate that the PVGIS web application can provide sufficiently accurate performance estimations of solar PV systems when the ERA5 dataset is used, only if the analyzed locations are completely unshaded.