The current study examined how individual differences in error-related brain activity might moderate the association between high trait neuroticism and internalizing symptoms. Data were collected from a sample of high-achieving young adults (N = 188) as part of a larger study on risk versus resiliency for psychopathology. Participants completed two behavioral tasks to elicit the error-related negativity (ERN): an arrow Flanker task and a Go/No-Go task. Analyses were constrained to two internalizing symptom dimensions of checking behavior and irritability. Contrary to expectations, ERN amplitude was not related to symptom severity at the bivariate level. However, ERN amplitude moderated the association between trait neuroticism and symptoms of ill temper, such that the neuroticism-irritability association was strongest among individuals with a blunted ERN. In addition, this finding was relatively consistent across tasks and across two complementary methods of scoring the ERN, suggesting an effect of ERN variance that is shared between tasks and that is relatively robust regarding processing differences. In all, the current study represents the first attempt to investigate how the ERN interacts with trait neuroticism to predict transdiagnostic symptom dimensions in adulthood.