Muscle cramping due to peripheral nerve hyperexcitability (PNH) is poorly characterized. This retrospective study examines the prevalence of PNH and response to treatment.The Duke EMG Database was queried to identify patients with muscle cramping tested for PNH from 2010 to 2015. Peripheral nerve hyperexcitability was defined by compound muscle action potential after-discharges on repetitive nerve stimulation. Response to treatment was determined by the treating physician's clinical impression 6 months after diagnosis or last documented visit.Seventy-two patients met inclusion criteria. Twenty-three (32%) patients had electrodiagnostic evidence of PNH. Of the patients with PNH, 74% had a good response to treatment whereas 37% of treated patients in the PNH-negative group (P = 0.0258). Carbamazepine and gabapentin were the most frequently used treatments with response rates of 70% and 77%, respectively.Muscle cramps associated with PNH respond well to symptomatic treatment, particularly with carbamazepine and gabapentin.