Idiopathic proctodynia, an enigmatic pain syndrome affecting the perianal region, can be persistent, relatively refractory to treatment, and associated with considerable psychological distress. The authors present the case of a patient with a long history of severe proctodynia that had been resistant to a range of topical and systemic treatments. With the use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% cream, the patient's pain resolved rapidly, leading to a substantially improved quality of life.