Vapor–liquid equilibrium data of six binary systems composed of ethylene glycol (EG), 1,2-propylene glycol (1,2-PG), 1,2-butanediol (1,2-BD), and 2,3-butanediol (2,3-BD) were measured and regressed by the NRTL model. With the binary interaction parameters regressed by experimental data, four separation processes for obtaining polymer-grade EG from the synthesis products were simulated, including a conventional distillation route, an azeotropic distillation route, a distillation route coupled with liquid−liquid extraction, and a reaction-assisted distillation route. The total annual costs and profits of the four routes were estimated and compared, which indicates that the annual profit was mainly determined by the yield of EG. The results also demonstrate that the reaction-assisted distillation route was proved to be the best strategy currently among those separation methods.