Background: Subclinical neurophysiologic abnormalities mainly suggestive of sensory fibers dysfunction were observed in some patients after 1 and 3 months of treatment with oral acitretin. Moreover, two cases of peripheral sensory neuropathy and one of sensorimotor polyneuropathy were observed after short‐term oral administration of this compound. Objective: The objective of this prospective study was to investigate whether short‐term treatment with oral isotretinoin can also affect peripheral nerve function. Methods: Serial neurologic and neurophysiologic examinations were performed on 18 young patients with severe nodulocystic acne prior to and 1 and 3 months after the onset of oral isotretinoin treatment (1 mg/kg per day). Results: Clinical neurologic examination before and under treatment disclosed no abnormalities in any of the patients. There were no significant differences between the pre‐ and post‐treatment neurophysiologic parameters. Furthermore, evaluation of the serial neurophysiologic measurements in each patient separately under oral isotretinoin treatment revealed no changes fulfilling the criteria of abnormality. Conclusions: Short‐term administration of oral isotretinoin in young patients does not cause clinical or subclinical neuropathy.