Thread compounds play an important role in the sealing ability of casing connections in the oil and gas industry. Next to their lubricating role during assembly, most of these thread compounds make use of nonbiodegradable or persistent particle additives to aid in the sealing ability. Replacing these additives for biodegradable and nonpersistent alternatives is, however, a challenge in high-temperature (>150◦C) well environments. This paper presents an investigation of the high-temperature failure mechanisms of thread compounds, with the aim of developing biodegradable high-temperature-resistant thread compounds. To this end, the performance of commercially available, environmentally acceptable thread compounds was investigated using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), high-temperature rheometry, and high-temperature pin-on-disk experiments. The compounds are assessed for their stability, consistency, lubricity, and the resulting wear at high temperature. The results indicated that, without exception, the commercially available thread compounds investigated in this study fail by adhesive and/or abrasive wear at approximately 150◦C because of thermally induced degradation. To remedy this and to validate the found failure mechanisms, a prototype thread compound was developed. The conclusion was that a successful high-temperature-resistant environmentally acceptable thread compound can be developed using the methodology described. The key property of this thread compound is the ability to form a tribofilm during makeup that protects the surface at a later stage when the lubricant has lost its consistency and the base oil is fully evaporated.