Purpose: To investigate the association between suboptimal serum vitamin D and early childhood caries (ECC) among children who received care at Seattle Children's Hospital (SCH) between 1999 and 2014.Methods: This cross-sectional study examined one- to six-year-old children in their primary dentition, with an American Society of Anesthesiologists (ASA) health status of II to IV, serum vitamin D, and dental data. Serum vitamin D was categorized as optimal (at least 75 nanomoles per liter) or suboptimal (less than 75 nanomoles per liter). Associations between serum vitamin D and caries were assessed using bivariate and multivariable (modified) Poisson regression models. Multivariable models were adjusted for age, race, ASA classification, season of vitamin D collection, and gastrostomy tube (G-tube) feeding status.Results: The mean age of 276 subjects was 3.4±1.5 years; 50.4 percent was female, 48.9 percent was Caucasian, 81.5 percent was ASA III status, 36.2 percent was G-tube fed, and 33.3 percent had ECC. Children with suboptimal 25-hydroxy vitamin D status were twice as likely to have ECC than children with optimal levels (relative risk = 2.14; 95 percent confidence interval = 1.45 to 3.16). The association between serum vitamin D and ECC was observed among children with neurologic (P<0.001) and genetic (P<0.001) conditions.Conclusions: Suboptimal 25-hydroxy vitamin D status was associated with increased risk for ECC in children with special health care needs. Interventions beyond the realm of the mouth are relevant for this highly vulnerable population and awareness of their vitamin D status should be considered.