Ranolazine modulates the cardiac voltage-gated sodium channel (NaV 1.5) and is approved by the FDA in the treatment of ischemic heart disease. Ranolazine also targets neuronal (NaV 1.7, 1.8) isoforms that are implicated in neuropathic pain. Therefore, we determined the analgesic efficacy of ranolazine in a preclinical animal model of neuropathic pain. Both intraperitoneal and oral administration of ranolazine dose-dependently inhibited the mechanical and cold allodynia associated with spared nerve injury, without producing ataxia or other behavioral side effects. These data warrant clinical investigation of the potential use of ranolazine in the treatment of neuropathic pain.