Optimizing synthesis factors of polyamide top layers is an important requirement in the design of thin film composite (TFC) membranes. In this research, the top layer fabrication method (conventional, heat curing, and spin coating), type of acid acceptor (sodium carbonate, sodium hydroxide, and triethylamine), type of organic phase solvent (hexane, heptane, and mixed hexane/heptane), and concentration of surfactant sodium dodecyl sulfate (0, 0.5, and 1 wt %) are selected as the control parameters of this synthesis and optimized using the Taguchi approach. The analysis of variance shows that the layer fabrication method is the most influential parameter on water flux and salt (NaCl) rejection of TFCs. Furthermore, although the type of organic solvent has not a significant contribution to the water flux, it is another significant factor affecting the rejection. The optimized membrane is then used to construct structureproperty relationships and to understand the influence of each individual factor on the desalination performance. Accordingly, a TFC membrane with the top layer fabricated by the heat curing method, in the presence of Na 2 CO 3 as the acid acceptor, hexane as the organic phase solvent and 0.5 wt % of the surfactant is prepared that shows water permeance of 2.73 L m −2 h −1 bar −1 and NaCl rejection of 98.1%. centration demonstrated the importance of these parameters in the preparation process of TFCs. The same group recently studied the synergistic effects of different additives on desalination properties of PA-TFC membranes. 23 The additives, which Additional Supporting Information may be found in the online version of this article.