Treatment and reuse of produced water (PW) from oil and gas operations could reduce water withdrawal in oil-and gas-producing regions, but its reuse remains limited because of the lack of price parity and complexity of the thermally driven and solvent-based separation processes required for treating hypersaline PW. More economical desalination of hypersaline PW can potentially be achieved with membrane distillation (MD) if the challenges of fouling and wetting of hydrophobic membrane materials can be overcome, and the membranes can be effectively cleaned and reused. In this work, we identified polytetrafluoroethylene (PTFE) as the best-performing membrane material among the three commercial membrane materials tested for MD of hypersaline PW from the Permian Basin, USA. PTFE membranes resisted pore wetting under operationally relevant test conditions. We also assessed the efficacy of a chemical cleaning protocol, which effectively removed the accumulated foulants from the PTFE surface but also likely altered PTFE properties, as the rate of subsequent membrane fouling increased. The results improve the understanding of the failure mechanisms of commercial hydrophobic membranes used for MD, and they inform the development of new membrane materials and cleaning protocols for MD of hypersaline PW. The results advance the prospects of MD desalination of hypersaline PW for reuse with its associated benefits like reducing disposal volumes and augmenting water supplies.