We sought to evaluate the interaction between repeated-course antenatal corticosteroids and inflammation gene polymorphisms with neurodevelopmental outcomes at age 2 years.We conducted nested case-control analysis of a randomized controlled trial of single- vs repeated-course antenatal corticosteroids. Cases had mental and/or psychomotor delay at age 2 years. Controls had normal neurodevelopment. Previous analyses of 125 cases and 147 controls identified 4 inflammation gene polymorphisms associated with neurodevelopmental delay at age 2 years.The interaction between repeated-course corticosteroids and the interleukin (IL)-6 –174 genotype with neurodevelopmental delay was significant (P = .046). The IL-6 –174 GG genotype was associated with neurodevelopmental delay at age 2 years in the single-course corticosteroid group (odds ratio, 6.47; 95% confidence interval, 1.86–22.50). Exposure to repeated-course antenatal corticosteroids abrogated this genotype effect (odds ratio, 1.30; 95% confidence interval, 0.48–3.54). Results were unchanged after controlling for potential confounders.Repeated-course antenatal steroids may reduce the increased risk of neurodevelopmental delay at age 2 years associated with IL-6 –174 GG genotype.