Organic Rankine Cycle (ORC) is an attractive option to utilize the low-grade waste heat for power generation. The selection of working fluid for ORC is a challenging task because of environmental constraints as most of the organic fluids has the capacity to damage the environment. In this research, a method for the selection of an optimum working fluid for the operation low grade waste heat is determined. The selection of the optimum working fluids depends upon the thermal efficiency, Global Warming Potential (GWP), Ozone Depletion Potential (ODP) and Atmospheric Lifetime of the fluid. Twelve different organic fluids including R134a, butene, R22, R152a, R245fa, R290, R161a, isobutene, isobutane, dimethyl ether, R600 and R124 are selected for the study. The ORC is analyzed by using EES at 2 MPa, 2.5 MPa and 3 MPa. The thermal efficiency of ORC is determined and is found that high operating pressure is favorable for the operation of ORC. At 2.5 MPa, the top three working fluids are R-245fa, R-600 and Iso-butene with an efficiency of 12.7%, 12% and 11.3% respectively. On the basis of thermal efficiency, R-245fa is the best but it has the highest GWP and atmospheric life of 1050 and 7.7 years. R-600 has GWP and atmospheric life of just 20 and 0.018 years. On the basis of environmental constraints, R-600 is found to be more beneficial than R-245fa. It is concluded that R-600 is the optimum working fluid for the operation of low-grade waste heat ORC.