Hollow fiber membranes with a multibore configuration have demonstrated their advantages with high mechanical strength, easy module fabrication, and excellent stability for membrane distillation (MD). In this work, the microstructure of multibore fibers was optimized for vacuum MD (VMD). A microstructure consisting of a tight liquid contact surface and a fully porous cross-section is proposed and fabricated to maximize the wetting resistance and VMD desalination performance. The new membrane exhibited a high VMD flux of 71.8 L m 22 h 21 with a 78 C model seawater feed. Investigations were also carried to examine various effects of VMD operational conditions on desalination performance. The 7-bore membrane showed higher flux and superior thermal efficiency under the VMD configuration than the direct contact MD configuration. Different from the traditional single-bore hollow fiber, the VMD flux of multibore membrane at the lumen-side feed configuration was higher than that of the shell-side feed due to the additional evaporation surface of multibore geometry.