OBJECTIVE : The Avon Longitudinal Study of Parents and Children (ALSPAC) and Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohorts were used to determine whether repeated exposure to gastroenteritis in early life could predict risk for psychiatric problems in childhood and in ALSPAC adolescents. We determined whether inflammatory biomarkers moderated the association between repeated gastroenteritis and mental health in adolescents from ALSPAC. METHODS : Episodes of gastroenteritis from birth to 30 and 36 months were reported by mothers. Psychological problems were assessed using the total difficulties and subscale scores on the Revised Rutter Parent Scale for Preschool Children at 42 months and the Strengths and Difficulties Questionnaire (SDQ) at 81 months in ALSPAC. Presence of psychiatric disorders at 15.5 years was assessed using the Development and Well-Being Assessment (DAWBA) in ALSPAC. In the MAVAN replication cohort, total difficulties were assessed on the SDQ at 60 and 72 months. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) at 9.5 years and CRP at 15.5 years were measured in ALSPAC participants. RESULTS : Repeated gastroenteritis associated with the total difficulties score in ALSPAC and MAVAN children. The β values were small, indicating that the clinical relevance of these findings requires further investigation. Repeated gastroenteritis was significantly associated with an increased prevalence of externalizing disorders at age 15.5 years, but odds ratios were small. CRP or IL-6 at 9.5 years or CRP at 15.5 years did not significantly moderate the association between repeated gastroenteritis and prevalence of psychiatric disorders. CONCLUSIONS : Identifying factors associated with vulnerability to psychopathology is key to early identification of individuals at risk.