Phantom limb syndrome (PLS) comprises various disturbances, including pain in the missing limb and phantom sensations. This study is about the successful treatment of a PLS patient by prolonged infusion of local anesthetic through a perineural catheter. A 45-year-old man came to the Rizzoli Orthopedic Institute (Bologna, Italy) complaining of a painful right leg after trauma. Complex regional pain syndrome (CRPS) type II was diagnosed. Therapy with tricyclics, gabapentin, and spinal infusion of morphine was started. After 4 years of treatment, infection led to the need for right below-the-knee amputation. After amputation, PLS appeared immediately and was not responsive to pharmacological treatment. At day II, a perineural sciatic catheter was positioned and 0.5% ropivacaine infusion with an elastomeric pump at 5 mL/h was started. The infusion was temporarily discontinued every week to evaluate the PLS. After 7 days, a 30% reduction in pain was observed, increased to 60% after 14 days, and disappeared completely after 21 days, leaving only the phantom limb sensations. After 28 days of continuous infusion, the phantom limb sensations had also disappeared. The perineural catheter was removed after 48 hours without perineural infusion. The patient was weaned from morphine over 150 days. Follow-ups at 6, 12, 24, and 36 months confirmed that the PLS did not reappear. The results are limited to one patient but are encouraging, particularly due to the relevance of the pathology and the poor results of conventional treatments. More cases are obviously needed to support the efficacy of this therapy.