A 2.5-year-old female spayed mixed breed dog was presented to Cornell University Emergency Service for progressive hind limb paralysis. The patient previously tested heartworm positive and a 3-dose schedule of melarsomine dihydrochloride was started approximately one month prior. Shortly after the last dose, the patient developed mild neurologic signs (difficulty wagging tail and climbing the stairs). The patient's neurologic status progressed to ambulatory paraparesis within several days. On presentation, the patient was paraplegic. Further neurologic examination revealed poor abdominal tone, and absent deep pain sensation in the pelvic limbs. Proprioceptive placing and hopping were normal in the thoracic limbs but absent in the pelvic limbs. The patient had normal patellar, withdrawal, and perianal reflexes with a mid-thoracic cutaneous trunci cut-off. Neurolocalization was consistent with a T3-L3 myelopathy. Magnetic resonance imaging findings revealed an extensive lesion of the spinal cord associated with severe intramedullary hemorrhage, most likely consistent with the diagnosis of myelomalacia. The theorized cause of the severe progressive myelomalacia was a rare complication of melarsomine dihydrochloride injections. Due to poor prognosis, the dog was euthanized and a necropsy was performed. This case report explores complications associated with melarsomine dihydrochloride treatment for heartworm disease, specifically examining secondary neurotoxicity to the injections, including a discussion on myelomalacia diagnosis, pathophysiology, treatment, and prognosis.