The performance and properties of thin film composite (TFC) membranes are controlled with several preparation variables such as chemistry of used polymers/additives and interfacial polymerization conditions. In this research an integrated statistic-systematic approach was developed to investigate the connection between desalination performance of the TFC Reverse osmosis (RO) membranes and interfacial polymerization condition using famous monomers i.e. m-phenylene diamine (MPD) and trimesoyl chloride (TMC). It was anticipated that statistic results could improve understanding of performance-synthesis relationships of TFC membranes. Effect of six key preparation factors on polyamide layer formation including: MPD, triethylamine (TEA), camphor sulfonic acid (CSA) and TMC concentrations; aqueous phase immersion time and organic phase immersion time were investigated to govern their optimum values and interactional effect on desalination performance. The prepared RO membranes were evaluated based on salt rejection and permeate flux. Two mathematical models were developed to correlate preparation factors by salt rejection and permeate flux. The TMC2, TEA and TEA x CSA were recognized as most effective terms on membrane flux and the most effective terms on rejection are the MPD x TMC, CSA(2), TMC2 and MPD. Reduction in immersion time of MPD led to improve in membrane flux. The results presented the significance of taking to account interactions between the desalination performance and the preparation conditions and once planning a policy to preparation TFC RO membranes for maximizing desalination performance. The optimum conditions for the RO process were MPD of 1.75 wt%, aqueous phase immersion time of 5.0 min, TEA of 3.0 wt%, CSA of 1.89 wt%, TMC of 0.26 wt% and organic phase immersion time of 1.0 min. The experimentally obtained flux and rejection efficiency (%) at optimum conditions were equal to 36.3 +/- 1.9 and 98.12 +/- 0.35%, respectively.