OBJECTIVES: To assess the association between burden experienced by caregivers of patients with fragile X syndrome (FXS) in the United States and a health state utilities index derived from the Aberrant Behavior Checklist-Community (ABC-C). METHODS: 340 US caregivers of children with FXS completed a questionnaire that captured information on FXS-related burden (i.e., specialist visits, medical tests, medications, financial burden, employment status, paid and unpaid caregiving, caregiver injuries, and mental health). Using the ABC-Utility Index (ABC-UI), an estimate of health-related quality-of-life derived from the ABC-C, five utility index categories were created: very low (0.00–0.33); low (0.34–0.66); moderate (0.67–0.77); high (0.78–0.89); and very high (0.90–1.00). After controlling for sex, age, overall ability level, and income, multivariable regression models documented the association between utility score and the nine burden-related outcomes. RESULTS: Respondents (283 with FXS male child; 57 with FXS female child) were mostly female (91%), Caucasian (92%), and married (84%), with mean age of 50 years. Approximately 2% of individuals with FXS were in the very low utility category, 30.6% low, 27.1% moderate, 37.6% high, and 2.6% very high. The mean utility score was 0.71. Females with FXS and adults ≥18 years had higher health utilities. Results from regression models indicate that increasing utility values reduced the likelihood of ≥5 (versus <5) specialist visits (b=-4.583; p<0.001) and ≥2 (versus 0 or 1) prescription medications used (b=-4.517; p<.001). Similarly, increasing utility score was associated with a decreased likelihood of ≥8 (versus <8) hours of unpaid caregiving (b=-2.723; p=0.003), ≥1 (versus 0 or 1) caregiver injuries (b=-7.540; p<0.001), and ≥1 (versus 0) mental health provider visits (b=-2.613; p=0.002). CONCLUSIONS: The ABC-UI appears to function well as a health-related quality-of-life indicator in individuals with FXS. Among caregivers of patients with FXS in the US, significant differences in burden exist across health state utilities.