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To examine whether a caregiver can provide reliable proxy quality of life (QOL) ratings of their adult significant other with a newly diagnosed high-grade glioma.This prospective QOL study was a companion protocol for 3 phase II high-grade glioma protocols. At study entry, 2 months, and 4 months after enrollment, 5 self-administered forms were completed by 197 patients and their caregivers to assess QOL.Caregiver ratings of QOL were available, respectively, for 92%, 93%, and 88% of baseline, 1st, and 2nd subsequent follow-up evaluations of patients who had completed their QOL assessments. There was a strong relationship between patient and caregiver QOL scores (Spearman and intraclass correlation coefficients greater than 0.5 for 87% and 80% of the measurements, respectively); however, for some measures (eg, the profiles of mood states short form) there was better agreement between patient and caregiver scores when the QOL scores were higher. There was good agreement between patient and proxy ratings independent of the cognitive function of the patient, except for the profiles of mood states short form with better correlation between patients and caregivers for those patients without cognitive impairment.In this multi-institutional prospective study there is a strong correlation between high-grade glioma patient and caregiver QOL scores, although for some measures this correlation is stronger for those patients without cognitive impairment. To improve the acquisition and the accuracy of assessing QOL status in high-grade glioma patients, proxy ratings from caregivers should also be obtained in conjunction with the patient, and consideration be given to substituting proxy ratings when a patient's self-report is absent.