Autism commonly aggregates in families, with twin studies estimating heritability to be around 80%. Subclinical autism-like characteristics have also been found at elevated rates in relatives of autistic probands. Physical and psychiatric conditions have been reported at elevated rates in autistic children and adults, and also in their relatives. However, to date, there has been no exploration of how aging may affect this pattern. This study examined cross-sectional data from the ongoing online PROTECT study. A total of 20,220 adults aged 50 years and older reported whether they have an autistic first-degree relative. In total, 739 older adults reported having an autistic first-degree relative (AFDR group) and 11,666 were identified as having no family history of any neurodevelopmental disorder (NFD group). The AFDR group demonstrated significantly higher frequencies of self-reported psychiatric diagnoses and a greater total number of co-occurring psychiatric diagnoses than the NFD group. Furthermore, the AFDR group reported elevated current self-report symptoms of depression, anxiety, traumatic experience, and post-traumatic stress than the NFD group. By contrast, few differences between AFDR and NFD groups were observed in physical health conditions, and no differences were observed in the total number of co-occurring physical health diagnoses. These findings suggest that adults who have an AFDR may be at greater risk of poor mental, but not physical, health in later life. Older adults with autistic relatives may benefit from close monitoring to mitigate this susceptibility and to provide timely intervention. Autism Res 2020, 13: 641-654. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Children and adults with an autistic relative have been found to experience more psychiatric difficulties than those with no family links to autism. However, a few studies have explored what happens when these individuals get older. Examining over 20,000 adults age 50+, we found that older adults with an autistic relative experienced elevated rates of most psychiatric conditions but not physical conditions. Older adults with autistic relatives may benefit from close monitoring to mitigate this susceptibility and to provide timely intervention.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Economic and Social Research Council. Grant Number: ES/P000703/1 National Institute for Health Research King's College London South London and Maudsley NHS Foundation Trust Biomedical Research Centrepublished version, accepted version (12 month embargo), submitted version