The development of high flux and solvent-stable thin-film composite (TFC) organic solvent nanofiltration (OSN) membranes was reported. A novel cross-linked polyimide substrate, consisting of a thin skin layer with minimum solvent transport resistance and a sponge-like sublayer structure that could withstand membrane compaction under high-pressure was first fabricated. Then the solvent flux was significantly enhanced without compromising the solute rejection by the coupling effects of (1) the addition of triethylamine/camphorsulfonic acid into the monomer solution, and (2) the combined post-treatments of glycerol/sodium dodecyl sulphate immersion and dimethyl sulfoxide (DMSO) filtration. Finally, the long-term stability of the TFC membrane in aprotic solvents such as DMSO was improved by post-crosslink thermal annealing. The novel TFC OSN membrane developed was found to have superior rejection to tetracycline (MW: 444 g/mol) but was very permeable to alcohols such as methanol (5.12 lm(-2)h(-1)bar(-1)) and aprotic solvents such as dimethylformamide (3.92 lm(-2)h(-1)bar(-1)) and DMSO (3.34 lm(-2)h(-1)bar(-1)). (c) 2014 American Institute of Chemical Engineers AIChE J, 60: 3623-3633, 2014