The objective of this study was to describe the use of retrograde gentamicin-coated tibial intramedullary nail (ETN PROtect™) in patients with tibial defects who required a tibiotalocalcaneal arthrodesis (TTC). Consecutive series case review of seven men treated with TTC using retrograde PROtect™ between January 2018 and December 2023. The main outcomes evaluated were fracture union, complications, and the health-related quality of life using the EuroQol five-dimension three-level questionnaire (EQ-5D-3L). The mean age was 45.3 8.0years. Six patients had a clinical history of chronic osteomyelitis, and one case underwent TTC for congenital pseudoarthrosis. Fracture union was achieved in 5 of 7 patients between 4 and 11months after surgery. Three patients developed complications; two patients had fistulas, and one had persistent pain. At the end of the follow-up, a median of 70 points (interquartile range: 60 to 90) on the EQ-5D-3L was reported. No complications directly attributed to the use of the PROtect™ were reported. TTC with retrograde PROtect™ is a prophylactic treatment option in patients with tibial defects treated with external fixation requiring a tibiotalar and subtalar arthrodesis. This novel use of PROtect™ allows simultaneous fixation of the tibiotalocalcaneal joint and protection of the regenerated bone, facilitating earlier rehabilitation in patients at high risk for postoperative infections.