Aim. To evaluate the impact of acetyl-L-carnitine (ALC) administration on the incidence and severity of sensory and motor paclitxel-induced peripheral neuropathy (PIPN) in patients with breast cancer. Methods. Prospective, randomized, controlled study. Patients presenting to the Clinical Oncology Department, Ain Shams University, Cairo, were assessed for eligibility. Forty eligible patients with breast cancer were randomized to one of 2 groups. Control group (n=20) received three cycles of paclitaxel on a weekly dose schedule. Test group received the same regimen plus 1000 mg of oral ALC 3 times/ day for 12 weeks. Baseline evaluation included clinical examination, nerve conduction velocity (NCV) and serum nerve growth factor (NGF) estimation. Incidence and severity of sensory and motor PIPN and treatment related toxicity were assessed after each cycle using the common terminology criteria for adverse events (CTCAE) version 4, (2010). Results. In the 1st cycle, no significant difference was evident between both groups in frequency of sensory and motor PIPN. In the 2nd cycle and in the 3rd cycle, test group showed a significantly lower frequency of; sensory neuropathy and motor neuropathy versus control. At baseline, the median NGF levels were significantly lower in test group versus control. At the end of the study the median NGF levels were significantly lower in the control group versus their initial baseline levels. While, the test group median levels were higher than their baseline levels. The delta change in NGF was significantly different between the 2 groups. Conclusion Acetyl-l-carnitine administration led to a reduction in the frequency of motor and sensory PIPN, an improvement in NGF levels and was accompanied with less side effects and.