Purpose <p>The Psychopathology in Autism Checklist (PAC) was developed to screen for mental health disorders in autistic adults with intellectual disabilities, focusing on identifying common mental health symptoms that do not overlap with autism characteristics. The current study aims to examine the factor structure and longitudinal measurement invariance of the PAC.</p> Methods <p>Existing data from a longitudinal multicentre study of mental health treatment in autistic individuals with intellectual disabilities were used. The PAC factor structure was examined using intake data (<i>n</i> = 201, 60 females, aged 13–68) and the longitudinal measurement invariance was explored using data across the study’s three time points (intake, end of treatment, follow-up; <i>n</i> = 173, 56 females, aged 13–68).</p> Results <p>The four disorder-specific subscales of the PAC (psychosis, depression, anxiety, obsessive-compulsive disorder [OCD]) showed an acceptable but suboptimal fit, while the inclusion of the general adjustment problems (GAP) subscale resulted in a poorer fit. Three of the subscales (GAP, OCD, depression) showed longitudinal measurement invariance, while two did not (psychosis, anxiety), suggesting caution when using the latter subscales for evaluative purposes. An alternative model was identified, comprising 35 of the original 42 PAC items. It showed an improved fit and longitudinal measurement invariance for all five subscales across the three time points.</p> Conclusion <p>These findings provide a starting point for further development of the PAC. While the alternative model appears to improve structural validity and seems better suited for comparisons over time, further research is needed to determine whether it could also be useful for screening purposes.</p>