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Membrane fouling, especially inorganic fouling due to salt crystal formation and deposition on the membrane surface, is still a major technical issue in membrane distillation (MD) applications. In this study, microbubble aeration (MBA) was included in a laboratory-scale vacuum membrane distillation (VMD) rig and its effect on a desalination process was examined. Without MBA, serious membrane scaling occurred during desalination of simulated high-salinity sea water (100 g.L−1 salt concentration), which resulted in a dramatic reduction of permeate flux to essentially zero after 120 min. Scanning electron microscopy showed that a layer of large cuboid salt crystals uniformly covered the membrane surface. However, membrane scaling was mitigated with the introduction of MBA, resulting in the improved VMD desalination performance, which was positively correlated with pump pressure in the microbubble (MB) generator. Results showed that the effective processing time of the VMD desalination processing cycle was respectively prolonged to 150, 180, and more than 300 and 360 min (cf. 120 min without MBA) when the pump pressure was respectively at 0.1, 0.2, 0.3 and 0.4 MPa, leading to the increase of cumulative water production. Further studies found that larger numbers of MBs of smaller size were produced at higher pump pressure, which are more beneficial for increasing water vapor production and alleviating salt precipitation. The difference in zeta potential between the MBs in distilled water (about −30 mV) and that in SW100 solution (about -2 mV) demonstrated that MBA not only effectively mitigated the negative effect of concentration polarization by enhancing the surface shear rate at the membrane surface, but also reduced salt precipitation probably due to the MBs attracting counterions to the gas-water interface. Finally, energy consumption analysis of the modified VMD desalination process revealed that MBA, while itself only adding about 3% to the total energy consumption at varied pump pressures, was able to improve the specific energy consumption, especially at higher pump pressures. Together, these results demonstrate that MBA is an effective way of improving the performance of VMD desalination of water.