The purpose of this study was to test the psychometric properties of the Caregiver Strain Questionnaire (CGSQ) among caregivers of children with autism. The CGSQ was originally developed to assess burden experienced by parents of children and adolescents with serious emotional and behavioral disorders. Study data was collected from 304 primary caregivers of children with autism using a cross-sectional survey design. We tested the one-, two-, and three-factor CGSQ model. Though the three-factor CGSQ model fit better than the one- and two-factor model, it was still short of an acceptable fit. Minor modifications were made to the three-factor model by correlating error terms. The modified three-factor CGSQ model with correlated error indicated reasonable fit with the data. The 21-item CGSQ had good convergent validity, as indicated by the correlation of its three subscales with constructs including mental health-related quality of life, maladaptive coping, social support, family functioning, and care recipient level of functional impairment and extent of behavioral problems, respectively. The internal consistency reliability of the instrument was also good, and there were no floor and ceiling effects. The CGSQ was found to be a reliable and valid instrument to assess burden among caregivers of children with autism.