The authors prospectively assessed drug reduction and patient satisfaction in 21 patients using vagus nerve stimulation (VNS) for refractory epilepsy and compared results to a case-matched control group with a mean follow-up of 13.2 months. Significant antiepileptic drug (AED) reduction occurred in 9/21 (42.9%) of VNS patients averaging 0.43 AED/patient, with dose reduction in four patients (19.0%). For 12/21 (57.1%) patients not reducing AED, dose reduction occurred in 6/21 (28.6%). Drug and dose reduction of AED is possible in patients using VNS for refractory epilepsy without loss of seizure control and with improved patient satisfaction.