Purpose <p>The co-morbidity of epilepsy in individuals with autism spectrum disorder has been reported as a wide range of 2.4% to 46%. The purpose of this study is to examine the relationship between epilepsy and autism in a novel, clinically relevant, and historically underrepresented cohort—youth hospitalized in a psychiatric setting.</p> Methods <p>Data was analyzed from the Autism Inpatient Collection, a multi-site study of youth with ADOS-2-confirmed autism hospitalized in specialized psychiatric units (<i>n</i> = 1354; age range 4–21.) Two-sample t-tests for continuous variables and Pearson’s chi square test for categorical variables were used to examine differences between two cohorts (autistic individuals with and without epilepsy) in age, sex, non-verbal IQ, co-morbidities, family history, genetic evaluation, and medication use.</p> Results <p>Criteria for epilepsy was met in 18.9% of participants. A high percentage of the sample had profound autism, with 72% having either intellectual disability, minimal verbal communication, or very low adaptive functioning scores. Presence of epilepsy was significantly associated with older age, lower non-verbal IQ, higher rates of genetic testing and significant results, first-degree family history of seizures, headaches, gastrointestinal problems, and a higher number of medications.</p> Conclusions <p>In this cohort of psychiatrically hospitalized autistic individuals, epilepsy prevalence and factors previously reported to be associated with epilepsy in autism were replicated. New associations with epilepsy were identified, including increased likelihood of prior genetic testing and pharmacologic burden. These results may inform providers regarding care of patients and counselling of families of autistic individuals seeking psychiatric care.</p>