426 patients with peripheral motor or sensory neuropathies were recruited and randomly assigned to 2 treatment groups in a double-blind, 30-day, prospective trial comparing L-acetylcarnitine (LAC) [1000 mg/day intramuscularly for the first 10 days then 2000 mg/day orally for the remaining 20 days] with placebo. Treatment efficacy was assessed by commonly employed electrophysiological tests performed at baseline and at the end of treatment. Safety and tolerability evaluations were performed on the entire patient population, although the statistical analysis for efficacy was restricted to the 298 patients with lower-than-normal nerve conduction velocities (CVs) at baseline. Among patients with impaired motor nerve function, a statistically significant improvement in mean CV (p < 0.01 vs placebo) was detected in LAC-treated individuals with mononeuropathies, whereas no statistical difference emerged between the LAC- and placebo-treated groups in patients with motor nerve poly neuropathies. In contrast, there were statistically significant differences between the LAC and placebo groups in terms of improvement in mean CV in patients with sensory nerve mononeuropathies (p < 0.05) and in those with sensory nerve polyneuropathies (p < 0.05). Only 17 patients reported poor tolerability to treatment, and only 7 of the 32 patients who were withdrawn from the study did so because of adverse events. Our trial demonstrated the efficacy of LAC in improving electrophysiological nerve conduction properties in patients with sensory or motor neuropathies.