After the 2011 Fukushima accident, seismic regulations for nuclear power plants (NPPs) in Japan have been strengthened to include countermeasures beyond design‐basis events. Therefore, the importance of seismic probabilistic risk assessments is a topic that deserves attention. Generally, uncertainty quantification has been a crucial undertaking to assess the fragility of NPP buildings. This study aims to quantify realistic uncertainties using a three‐dimensional (3D) finite element (FE) model to reflect the obtained results to the conventional simple sway‐rocking (SR) model, and to develop a seismic fragility assessment method that considers 3D effects. As a first step, a 3D FE model was developed, and a seismic response analysis was performed to evaluate the seismic response of the buildings. For comparison, a seismic response analysis using the conventional SR model was performed. For input ground motions, 200 types of simulated seismic ground motions, generated using fault‐rupture models were adopted. As a second step, two types of uncertainties are evaluated for uncertainty quantification: uncertainty for input seismic ground motion and that due to different locations of equipment installed on a floor. As a third step, to reflect the 3D effect on the uncertainty of the conventional SR model, were investigated the median and logarithm standard deviation of the response ratio (3D FE/SR) of the maximum acceleration of the two models. The results of epistemic uncertainty tended to increase with the increasing elevation level and the epistemic uncertainty result in the basement floor, where important equipment was installed, was relatively small. By reflecting this epistemic uncertainty into the conventional SR model, a more realistic fragility assessment that considers the 3D effect is expected by applying this result as epistemic uncertainty of the SR model of the fragility assessment.