Advances in orthopaedic surgery include the expanded indications of intramedullary fixation. The inherent biomechanical advantages of the tibiotalocalcaneal retrograde intramedullary nail (TTCA-RIMN) make it an extremely useful tool to achieve extended ankle arthrodesis in arthritic conditions and in Charcot deformities. However, when infection arises with intramedullary devices, successful treatment depends on aggressive irrigation, debridement and delivery of antibiotics, and stabilization. This paper describes the technique of using a retrograde intramedullary nail constructed from antibiotic-impregnated polymethylmethacrylate cement that achieves bone debridement, internal stabilization, and the local delivery of antibiotics to the site of infection, with minimal systemic or local toxicity. This technique has proven successful in the treatment of the infected extended ankle arthrodesis after retrograde intramedullary nailing, especially in compromised patients, with retention of limb function in situations that would otherwise require an amputation.