OBJECTIVE: To measure the co-morbidities associated with Down syndrome compared with those in other children with special health care needs (CSHCN). Additionally, to examine reported access to care, family impact, and unmet needs for children with Down syndrome compared with other CSHCN. STUDY DESIGN: An analysis was conducted on the nationally representative 2005 to 2006 National Survey of Children with Special Health Care Needs. Bivariate analyses compared children with Down syndrome with all other CSHCN. Multivariate analyses examined the role of demographic, socioeconomic, and medical factors on measures of care receipt and family impact. RESULTS: An estimated 98,000 CSHCN have Down syndrome nationally. Compared with other CSHCN, children with Down syndrome had a greater number of co-morbid conditions, were more likely to have unmet needs, faced greater family impacts, and were less likely to have access to a medical home. These differences become more pronounced for children without insurance and from low socioeconomic status families. CONCLUSIONS: Children with Down syndrome disproportionately face greater disease burden, more negatively pronounced family impacts, and greater unmet needs than other CSHCN. Promoting medical homes at the practice level and use of those services by children with Down syndrome and other CSHCN may help mitigate these family impacts.