OBJECTIVES: To describe the burden of illness associated with neural tube defects (NTDs) in Germany from a payer perspective. METHODS: Retrospective data of patients with Spina Bifida (SB) and Encephalocele were analyzed using 2006-2009 German health insurance fund data (Techniker Krankenkasse). Patients were identified using ICD10 codes, data assessed included outpatient and inpatient care, rehabilitation, remedies and medical aids, and use of pharmacotherapy. The analysis was stratified by age group to provide a lifetime burden estimate and was compared to standardized health care expenditures from the German Risk Compensation Scheme (RSA) to obtain an indicator of incremental burden due to NTD. RESULTS: Overall, 4,173 patients were identified, 47.2% of whom were male and 95% had SB. 19.6% and 17.5% patients had an additional diagnosis of depression and incontinence  respectively. Costs of patients with SB and Encephalocele were substantially higher than general population in all age strata. The difference was highest for patients ≤10 years old (€10,775 vs. €2,360 for ≤1 year olds, €8,398 vs. €833 for 2-5, and €10,686 vs. €863 for 6-10) and smallest for 41-50 (€2,596 vs. €1,101) and 71+ group (€5,256 vs. €4,389). Inpatient care contributed 78% of total cost for patients 0-1, whereas remedies and medical aids accounted for 60% of total cost for patients 2-5 and 6-10. Among sub-groups, costs of patients with Spina Bifida and Hydrocephalus were highest, especially in the first 10 years of life. CONCLUSIONS: The burden of NTD in Germany is substantial and continues throughout the patient life in terms of the level of health care expenditures and relative to overall population. Efforts should be devoted to improving prevention of NTDs and providing appropriate support for patients, parents, and caregivers, especially in early years.