Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social behavior. One possible explanation for social communication deficits in ASD could be differences in biological systems that support responses to environmental stimuli. If so, it is unclear if differences in the arousal response to social stimuli in ASD are due to reduced interest in social information, or to an increased stress response. The hypothalamic pituitary adrenal axis facilitates arousal and the stress response to sensory input, including social stimuli. Previous research shows blunted cortisol response to social evaluative threat in children with ASD. The majority of prior work has focused on children with ASD, but adolescents with ASD are understudied. The adolescent period is of interest, as this developmental epoch is associated with increased salience of social evaluative threat in typically developing (TD) populations. In this study, we employed the Trier Social Stress Test (TSST), a laboratory paradigm that involves exposure to social evaluative threat, to study the cortisol and behavioral response to social evaluative threat in ASD and TD adolescents. Salivary cortisol data were collected at six time points before and after the TSST. Behavioral data were collected using video recordings of the TSST, which were then operationalized and coded. Paired sample t-tests were used to calculate within-group cortisol response to the TSST. Cortisol significantly increased in response to the TSST in the TD group but not the ASD group. The TD group showed a trend for more self-soothing behaviors during the stressor than the ASD group. The lack of a cortisol response to the TSST in the ASD group suggests that the TSST is not interpreted as stressful or salient for ASD adolescents. Autism Res 2017, 10: 346-358. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.