The correct calculation of cell void fraction is pivotal in accurate simulation of two‐phase flows using a computational fluid dynamics‐discrete element method (CFD‐DEM) approach. Two classical approaches for void fraction calculations (i.e., particle centroid method or PCM and analytical approach) were examined, and the accuracy of these methodologies in predicting the particle‐fluid flow characteristics of bubbling fluidized beds was investigated. It was found that there is a critical cell size (3.82 particle diameters) beyond which the PCM can achieve the same numerical stability and prediction accuracy as those of the analytical approach. There is also a critical cell size (1/19.3 domain size) below which meso‐scale flow structures are resolved. Moreover, a lower limit of cell size (1.63 particle diameters) was identified to satisfy the assumptions of CFD‐DEM governing equations. A reference map for selecting the ideal computational cell size and the suitable approach for void fraction calculation was subsequently developed. © 2014 American Institute of Chemical Engineers AIChE J, 60: 2000–2018, 2014