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Anxiety and depression co-occur in 50–70% of adults with autism spectrum disorder (ASD) but treatment methods for these comorbid problems have not been systematically studied. Recently, two ASD-tailored protocols were published: mindfulness based stress reduction (MBSR) and cognitive behavioural therapy (CBT). We wanted to investigate if both methods are equally effective in reducing anxiety and depression symptoms among adults with ASD. 59 adults with ASD and anxiety or depression scores above 7 on the Hospital Anxiety and Depression Scale, gave informed consent to participate; 27 followed the CBT protocol, and 32 the MBSR treatment protocol. Anxiety and depression scores, autism symptoms, rumination, and global mood were registered at the start, at the end of the 13-week treatment period, and at 3-months follow-up. Irrational beliefs and mindful attention awareness were used as process measures during treatment and at follow-up. Results indicate that both MBSR and CBT are associated with a reduction in anxiety and depressive symptoms among adults with ASD, with a sustained effect at follow-up, but without a main effect for treatment group. A similar pattern was seen for the reduction of autistic symptoms, rumination and the improvement in global mood. There are some indications that MBSR may be preferred over CBT with respect to the treatment effect on anxiety when the scores on measures of irrational beliefs or positive global mood at baseline are high. Mindfulness and cognitive behavioral therapies are both promising treatment methods for reducing comorbid anxiety and depression in adults with ASD.