(2015), Theoretical study of zonal differences of electron density at midlatitudes with GITM simulation, J. Geophys. Res. Space Physics, 120, 2951-2966, doi:10.1002 The copyright line for this article was changed on 27 AUG 2015 after original online publication.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Abstract This study investigated various physical processes responsible for the longitudinal modulation of electron density (Ne) at midlatitudes by employing the global ionosphere-thermosphere model (GITM). The good agreements between GITM outputs and CHAMP observations indicate that the model is a suitable tool to perform the theoretical study. Nine runs were carried out to determine the effects from geomagnetic field geometry, zonal wind, meridional wind, high-latitude activity, migrating tides from the lower atmosphere, and solar illumination in quantitative ways. Distinct features were discussed as follows. It was crucial that the geomagnetic and geographical axes were offset for the development of the longitudinal difference of Ne. The zonal wind contributes to about 80% of the fraction of the observed longitudinal dependence of Ne. The meridional wind effect is out of phase with the zonal wind over North America and Southern Ocean regions, which trims the fraction of the longitudinal difference to 65%. Over the South Pacific Ocean, the nighttime Ne maintains at a higher level because of in-phase effects from both zonal and meridional winds. The solar illumination was important in the formation of the background longitudinal pattern of the electron density. The migrating tide from the lower atmosphere could enhance the longitudinal difference of Ne by 15% over North America. Enhanced activities at high latitudes could alter the longitudinal pattern of Ne by transporting thermospheric composition disturbances to midlatitudes.