A facile large scale synthesis developed for high pure iohexol 1 using an inexpensive synthetic route consist a total of 6 steps and easily isolatable intermediates. Key to the strategy is the preparation and isolation of 5-[N-(2,3-Dihydroxypropyl)acetamido]-2,4,6-triiodo-N,N'-bis(2,3-dihydroxypropyl)isophthalamide (crude iohexol, 9) in good yield using an efficient and practical protocol. The main advantages of the route include a straight forward reaction sequence and good overall yields at every stage. The process impurities have been well controlled without using any resins. Two best methods have proposed to eliminate o-acetyl and process impurities. The structures of all intermediates were confirmed by ¹H-NMR, ¹³C-NMR, IR and MS and HPLC.