Diagnosing autism spectrum disorder (ASD) in adulthood often represents a challenge in clinical practice. The aim of the present study was to evaluate the sensitivity and specificity of the ADOS and ADI-R in diagnosing ASD in adults. 113 subjects with an IQ of 70 or above were assessed through an extensive clinical evaluation. The ADOS-2 Module 4 and the ADI-R were separately administered by staff members blind to clinical judgment. Our results cautiously confirm the accuracy of ADOS-2 Module 4, while suggest that ADI-R might not be reliable in adults without intellectual disability. Clinicians' training and experience remains of primary importance while assessing adults who could potentially belong to the autism spectrum.