A large number of youngsters with autism spectrum disorders (ASD) display comorbid attention deficit/hyperactivity disorder (ADHD) symptoms. However, previous studies are not conclusive whether psychophysiological correlates, like cardiac reactivity, are different for ASD with comorbid ADHD (ASD+) compared to ADHD. Therefore, the current study investigated (dis)similarities in cardiac reactivity and attention task performance. In a clinical sample, adolescents diagnosed with ASD+ (n = 20) versus ADHD (n = 36) and stimulant medication use (56 %) were compared during a baseline with eyes closed and task performance. Results for cardiac reactivity were similar for both diagnostic groups. Stimulant-medicated adolescents showed decreased adaptation of LF/HF ratio and faster reaction times than stimulant-free adolescents. The current study underlines the psychophysiological overlap of ADHD symptoms in adolescents with ASD+ and adolescents with ADHD.