Pediatric cyclic vomiting syndrome (CVS) is associated with a high prevalence of co-morbid migraine and other functional disorders, and with two adult migraine-associated mitochondrial DNA (mtDNA) polymorphisms: 16519T and 3010A. These potential associations have not been studied in adult CVS. The objective of this study is to determine the prevalence of 16519T and 3010A mtDNA polymorphisms and other functional disorders in adult CVS patients. Adults with CVS recruited from the University of Kansas meeting Rome III criteria and a population control group completed a self-reported survey that included questions relating to the diagnostic criteria for several functional disorders. DNA was isolated from blood or saliva and genotyping was performed by standard methodologies. Adult CVS subjects, compared to controls, had significantly more symptoms consistent with several other functional disorders. 16519T was present in 22/31 cases (71%) of child-onset (<12 years) and 9/31 (29%) cases of adult-onset (18+ years) CVS (P = 0.01), vs 27% of controls. Among subjects with 16519T, 3010A was present in 30% of child-onset vs 0% of adult-onset CVS (P = 0.05) and 2% of controls. The conclusions drawn were: (i) unlike pediatric CVS, adult CVS is not associated with the 16519T and 3010A mtDNA polymorphisms, suggesting a degree of genetic distinction and (ii) similar to the pediatric setting, adult CVS is associated with a substantial burden of co-morbid functional disorders.