The aim of the present study was to establish diagnostic validity of the new algorithm of the Autism Diagnostic Observation Scale, the ADOS-2, to differentiate between ASD and other clinically relevant psychiatric and developmental disorders in a large German sample. Validity of ADOS and ADOS-2 diagnostic algorithms was established in 826 individuals (n = 455 autism, n = 216 autism spectrum, n = 155 non-ASD patients) by receiver operating curves. Confidence intervals overlapped largely for ADOS and ADOS-2 algorithms, confirming diagnostic validity of both algorithms. Adding information of the Social Communication Questionnaire and the Social Responsiveness Scale resulted in slightly improved classification rates for autism in Module 4. We thus replicated previous findings of the diagnostic validity of the ADOS-2 algorithms.