National estimates of hospitalization diagnoses and costs were determined using the 2016 HCUP Kids' Inpatient Database. Children and youth with autism were hospitalized over 45,000 times at over $560 million in costs and 260,000 inpatient days. The most frequent principal diagnoses for hospitalizations of children and youth with autism were epilepsy, mental health conditions, pneumonia, asthma, and gastrointestinal disorders, which resulted in almost $200 million in costs and 150,000 inpatient days. Mental health diagnoses accounted for 24.8% of hospitalizations, an estimated $82 million in costs, and approximately 94,000 inpatient days. Children and youth with autism were more likely hospitalized for epilepsy, mental health diagnoses, and gastrointestinal disorders, and less likely for pneumonia and asthma compared to other children and youth.