Background: An association has been described between mortality in children with meningococcal disease and functional polymorphisms in the interleukin-1 (IL1) cluster. We undertook a multicenter study to evaluate associations of these polymorphisms in a Central European population. Patients and Methods: The study involved 95 Middle European pediatric hospitals. We collected blood samples from, and clinical information about, 285 previously healthy children with meningococcal infection. We used a newly developed multiplexed mutagenic separated PCR assay to analyze 6 polymorphisms within the IL1 cluster: IL1A (؊889)C/T, IL1A (؉4845)G/T, IL1B (؊511)C/T, IL1B (؊31)C/T, IL1B (؉3954), and IL1RA (؉2018)C/T. We studied the same polymorphisms in a comparison group of 481 healthy newborns. Results: Genotype frequencies between patients and the comparison group differed significantly only for the IL1RA (؉2018)C/T variant: The CC genotype was more frequent in patients (11%) than in healthy controls (5%; P ؍ 0.008). In the patient group, the C allele was significantly more prevalent (67%) in nonsurvivors than in survivors (42%; P ؍ 0.02). Conclusion: The IL1RA (؉2018)C/T polymorphism is associated with the risk of meningococcal disease and with its outcome.