The S allele of the 5-HTTLPR has been associated with anxiety-related behavioural traits and harm avoidance. The 5-HTTLPR polymorphism is suggested to modulate the serotonergic response to stress, meaning that individuals carrying the SS genotype who have significant stress histories may tend to develop depressive symptoms. In the Mannheim Study of Risk Children, which followed a cohort of n = 384 from birth to adolescence, the association of 5-HTTLPR with harm avoidance and internalising problems was examined, including gender and early life stress as possible moderators. Child and adolescent characteristics were assessed using the Junior Temperament and Character Inventory, the Child Behaviour Checklist and the Youth Self Report. Early life stress was determined by a risk index measuring the presence of 11 adversity factors. Results did not reveal an association with 5-HTTLPR genotype. There were no moderating effects of early life stress or gender. An explanation for the negative findings is that the S allele may be a necessary but not sufficient component cause in a composite risk factor.