Separation of oxygen isotopic water using a newly developed pressure-driven air gap membrane distillation (AGMD) process that is applicable to a multistage MD system was investigated. Pressure-driven (PD) AGMD is distinguished from a currently available AGMD by way of its permeation flux generation. It uses a peristaltic pump to generate the pressure gradient oil the membrane interface. Permeation characteristics and isotopic selectivity of four different hydrophobic membranes were evaluated. Permeation fluxes under the various conditions were measured by weighing the collected membrane-permeated water. Permeation fluxes for PD AGMD were higher than those of AGMD as much as 4.2-fold whereas the degree of isotope selectivity was competitive. The oxygen isotopic concentrations of the samples were analyzed by measuring the isotopic ratio (H2O)-O-18/(H2O)-O-16 using tunable diode laser absorption spectroscopy and isotopic ratio mass spectrometer. A multistage PD AGMD system was also successfully constructed and operated.