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To perform a large registry-based study to determine the relative prevalence of gastrointestinal (GI) problems in children with an autism spectrum disorder (ASD) from families with multiple affected members compared with their unaffected sibling(s).In-home structured retrospective medical history interviews by parent recall were conducted by a pediatric neurologist. Our analysis sample included information about GI health of 589 subjects with idiopathic, familial ASD and 163 of their unaffected sibling controls registered with Autism Genetic Resource Exchange. Individuals with ASD were subgrouped into 3 autism severity groups (Full Autism, Almost Autism, and Spectrum) based on their Autism Diagnostic Interview—Revised and Autism Diagnostic Observation Scale scores.Parents reported significantly more GI problems in children with ASD (249/589; 42%) compared with their unaffected siblings (20/163; 12%) (p < .001). The 2 most common Gl problems in children with ASD were constipation (116/589; 20%) and chronic diarrhea (111/589; 19%). Conditional logistic regression analysis showed that having Full Autism (adjusted odds ratio [AOR] = 14.28, 95% confidence interval [CI]: 6.22–32.77) or Almost Autism (AOR = 5.16, 95% CI 2.02–13.21) was most highly associated with experiencing GI problems. Increased autism symptom severity was associated with higher odds of GI problems (AOR for trend = 2.63, 95% CI: 1.56–4.45).Parents report significantly more GI problems in children with familial ASD, especially those with Full Autism, than in their unaffected children. Increased autism symptom severity is associated with increased odds of having GI problems.