The airlift external circulation membrane bioreactors (AEC-MBRs) have been attracting attentions due to their capabilities of nutrient removal with lower energy demand and smaller footprint. The gap between laboratory study and full-scale AEC-MBRs regarding hydrodynamics needs to be addressed. In this study, impacts of seven design variables and cyclic aeration modes on hydrodynamics were studied for the scale-up of AEC-MBRs with computational fluid dynamics modelling. The results demonstrated that shear stress on membranes was 14.7% higher in full-scale MBR with only 15% of SAD(m) of lab-scale MBR while it showed an overall higher sensitivity to the design variables in lab-scale MBRs. Cyclic aeration modes created a sinusoidal pattern of shear stress and generated more fluctuations and were expected to reduce more irreversible fouling. When a shifting frequency of 5 s/5 s was applied in AEC-MBR, 50% of aeration energy was reduced and yield water with good quality was harvested.