It remains unclear why individuals with autism spectrum disorder (ASD) tend to respond in an atypical manner in social situations. Investigating autonomic and subjective responses to social vs. nonsocial stimuli may help to reveal underlying mechanisms of these atypical responses. This study examined autonomic responses (skin conductance level and heart rate) and subjective responses to social vs. nonsocial pictures in 37 adolescents with an ASD and 36 typically developing (TD) adolescents. Thirty-six pictures from the International Affective Picture System were presented, divided into six categories based on social content (social vs. nonsocial) and pleasantness (pleasant, neutral, and unpleasant). Both in adolescents with ASD as well as TD adolescents, pictures with a social content resulted in higher skin conductance responses (SCRs) for pleasant and unpleasant pictures than for neutral pictures. No differences in SCRs were found for the three nonsocial picture categories. Unpleasant pictures, both with and without a social content, showed more heart rate deceleration than neutral pictures. Self-reported arousal ratings were influenced by the social and affective content of a picture. No differences were found between individuals with ASD and TD individuals in their autonomic and subjective responses to the picture categories. These results suggest that adolescents with ASD do not show atypical autonomic or subjective responses to pictures with and without a social content. These findings make it less likely that impairments in social information processing in individuals with ASD can be explained by atypical autonomic responses to social stimuli. Autism Res 2014, 7: 17–27. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.