In this paper, an experimental investigation is conducted to present a new cascade of the air gap membrane distillation (AGMD) for enrichment of (H2O)-O-18 in natural water. The isotopic separation capability of the poly(vinylidene fluoride) (PVDF) nanofibrous membrane is compared with the conventional ploy(tetrafluoroethylene) (PTFE). To achieve this, appropriate PVDF electrospun membranes were prepared and applied in AGMD process to enrich (H2O)-O-18 in natural water. Then, the theoretical cascade calculation is performed to obtain operational parameters such as arrangement of the cascade and the maximum enrichment. The simulated cascade is examined for the enrichment of (H2O)-O-18 by PVDF membranes. The enrichment performance of the process the new cascade with 10 AGMD separation stages is implemented to increase. The results indicate that (H2O)-O-18/(H2O)-O-16 isotopomeric separation factor increases through using PVDF nanofibrous membrane. The significant increase (more than 30%) is occurred in (H2O)-O-18 concentration in the final product of AGMD cascade system. The findings suggest that the PVDF nanofibrous membrane performs better in the isotopomeric separation and presents superior cut-off value (around 85%) compared to commonly employed PTFE commercial membrane. (C) 2015 Elsevier B.V. All rights reserved.