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Aggression remains a major cause of morbidity in patients with autism spectrum disorder (ASD). Current pharmacotherapy for aggression is not always effective and is often associated with morbidity. Nicotinic acetylcholinergic neurotransmission may play a prominent role in ASD pathophysiology based on human and animal studies, and preclinical studies show nicotine administration can reduce aggression-related behaviors. Transdermal nicotine has been used to treat agitation in neuropsychiatric conditions with cholinergic dysfunction. Here we report the use of transdermal nicotine as an adjunctive medication to treat aggression in a hospitalized adolescent with ASD. Nicotine patch was recurrently well tolerated, and reduced the need for emergency medication and restraint. These findings suggest further study of transdermal nicotine for aggression comorbid with ASD is warranted.