Poly(oxymethylene)　dimethyl　ethers　(PODEn)　is　a　promising　excellent　additive　for　diesel　fuels.　The　PODEn　production　by　traditional　reactor　conform　to　Schulz　-　Flory　distribution　resulting　in　low　product　yield　and　large　circulating　material　flow,　which　leads　to　high　energy　consumption　and　cost.　This　study　presents　a　novel　reactive　distillation　(RD)　process　for　the　PODEn　synthesis　by　polymerization　reaction　from　trioxane　and　methylal.　A　rigorous　simulation　model　of　the　RD　process　was　developed　for　the　plant　design　and　scale-up.　Also,　a　sensitivity　analysis　was　performed　to　determine　the　influence　of　key　operating　parameters　on　the　RD　process　performance.　The　production　composition　analysis　indicates　that　the　RD　process　can　effectively　control　the　degree　of　polymerization　and　obtain　high　selectivity　for　any　target　product(s).　The　techno-economic　analysis　shows　that　the　process　is　feasible,　with　over　96%　and　13%　reduction　in　CapEx　and　OpEx,　over　68%　savings　in　total　annual　costs　as　compared　to　the　reaction-separation　technology.　Higher　conversion　and　selectivity　can　be　obtained　by　RD,　within　lower　recirculation　rate　(only　12281　kg/h　instead　of　2950　kg/h)　as　compared　to　the　conventional　process.