Dramatic fluctuations in gas compositions will affect end-users. At current stage, studies on interchangeability indices, which are commonly utilized to characterize the interchangeability of natural gas, can resolve the dilemma. However, the existing studies mainly focused on conventional atmospheric burners, and it tends not to be suitable for fully premixed appliances because of different combustion characteristics. In this paper, an experimental system of fully premixed burners was built up to verify the applicability of interchangeability combinations, and the equivalent gas was mixed by H-2, N-2, and i-C4H10. Five sets of double indices combinations were theoretically selected within a relative error of +/- 5% compared to the reference gas. The adaptability of several equivalent gas was quantified by energy efficiency indices, combustion performances, and flue gas emissions. It is found that (W-s, H-i) can be used as gas interchangeability indices for fully premixed burners better than (W-s, V-0), because thermal efficiency of (W-s, H-i) changed within 3%. (W-s, CP) can only work on gas appliances equipped with low-pressure injectors. Moreover, the utilization of (H-i, S-n) and (V-0, S-n) would decrease the thermal efficiency by 18% and it should be avoided. This work can provide a guidance to supplement technical gaps in interchangeability studies of fully premixed appliances.