PURPOSE: Muscle cramping due to peripheral nerve hyperexcitability (PNH) is poorly characterized. This retrospective study examines the prevalence of PNH and response to treatment. METHODS: 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. RESULTS: 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. CONCLUSION: Muscle cramps associated with PNH respond well to symptomatic treatment, particularly with carbamazepine and gabapentin.