Fischer-Tropsch Synthesis (FTS) is a primary pathway for gas-to-liquid (GTL) technology. In order to overcome commercial problems associated with reaction and transport phenomena, the use of supercritical solvents has been proposed to enhance conversion, catalyst stability and improve temperature control in fixed-bed reactors. One of the major challenges in designing the supercritical FTS reactor unit is selecting appropriate solvents of critical properties within the required reaction operating conditions. Numerous alternatives exist and should be screened based on relevant criteria. The main aim of this paper is to develop a screening methodology to identify an optimum supercritical solvent or a mixture of solvents that meet the aforementioned criteria while minimizing the cost and more importantly satisfying the safety constraints. A safety metric system was developed in order to compare the risk issues associated with using different solvents. In addition, an economic analysis of using the different solvents was performed. Finally, a case study was solved to illustrate the use of the proposed metrics and the selection of solvents based on safety and techno-economic criteria. (C) 2012 Elsevier Ltd. All rights reserved.