With the annual global electricity production exceeding 30,000 TWh, the safe transmission of electric power has been heavily relying on SF 6 , the most potent industrial greenhouse gas. While promising SF 6 alternatives have been proposed, their compatibilities with materials used in gas-insulated equipment (GIE) must be thoroughly studied. This is particularly true as the emerging SF 6 alternatives generally leverage their relatively higher reactivity to achieve lower global warming potentials (GWPs). Here, a high-throughput compatibility screening of common GIE materials was conducted with a representative SF 6 alternative, namely, C 4 F 7 N (2,3,3,3-tetrafluoro-2-(trifluoromethyl)propanenitrile)/CO 2 gas mixtures. In this screening, the insulation performance of C 4 F 7 N/CO 2 gas mixtures, as an indicator of the C 4 F 7 N/materials compatibility level, was periodically monitored during the thermal aging with tens of materials from SF 6 -insulated GIE, including desiccants/adsorbents, rubber, plastics, composites, ceramics, metals, etc. The identification of incompatible materials and the follow-up mechanism studies suggested that the acidity of materials represents the primary cause for C 4 F 7 N/materials incompatibility when C 4 F 7 N/CO 2 gas mixtures are used as a drop-in replacement solution for existing SF 6 -insulated apparatuses. Mitigation strategies tackling the acidity of materials were then proposed and validated. Additionally, the amphoteric characteristics of C 4 F 7 N were briefly discussed. This work provides insight into the materials incompatibility of SF 6 alternatives, along with validated mitigation strategies, for the selection and design of materials used in future eco-friendly GIE.