OBJECTIVES: Financial considerations may impact the pregnancy decisions of expectant parents who receive a positive prenatal screening test result for Down syndrome (DS).  This study estimates the out-of-pocket health care costs for parents associated with raising a child with DS between birth and 18 years of age, using private U.S. health insurance data.  METHODS: Patients with a diagnosis of DS (ICD-9-CM 758.0x) who were enrolled in their family insurance plan as a child and had an identifiable parent were identified from the OptumHealth Reporting and Insights administrative claims database.  A patient’s observation time was divided into clinically relevant age categories for DS.  Patients with DS in each age category were matched to controls without diagnoses for chromosomal conditions.  Mean annual health care utilization costs were compared between the patient-age cohorts with DS and matched controls using Wilcoxon signed-rank tests.  RESULTS: After matching, patient-age cohorts were statistically similar with respect to most demographic and family characteristics.  However, patients with DS had significantly higher mean annual out-of-pocket costs than their matched controls within each age and cost category.  Total annual incremental costs were highest among patients with DS from birth to age 1 ($1,907, p<0.001), when the need for surgery is greatest.  The greatest incremental costs were inpatient costs in the first year of life ($925, p <0.001) and outpatient costs in later years (ranging from $623-$183, all p<0.001).  Overall, patients with DS incurred incremental out-of-pocket medical costs of $18,248 between birth and age 18 years.  CONCLUSIONS: Across all age categories, mean total out-of-pocket annual costs for parents were greater among individuals with DS compared to their matched controls.  On average, parents of children with DS pay an additional $84 per month for out-of-pocket medical expenses when costs are amortized over 18 years.