This study examined psychometric properties of a brief version of the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) among persons with traumatic brain injury (TBI) and the relations of the WHOQOL-BREF domains, including physical capacity, psychological wellbeing, social relationships, and environment, to different indicators of TBI severity. Of the 354 eligible and available subjects from 22 hospitals in northern Taiwan over a 6-month period, 199 completed telephone interviews during data collection. Three indicators of TBI severity were used: the Glasgow Coma Scale, the presence of post-traumatic amnesia, and the abbreviated injury scale to the head. All domain scores of the WHOQOL-BREF had nearly symmetrical distributions: low percentages of ceiling and floor values (0-3%), low missing rates (0-0.5%) for all but one item (43.2%), and very good internal consistency (0.75-0.89) and test-retest reliability (0.74-0.95). The WHOQOL-BREF also exhibited excellent known-groups validity, as well as very good responsiveness and convergent validity with regard to employment, independence in daily life activities, social support, and depression. After adjustment for potential confounders, almost none of the domain scores of the WHOQOL-BREF significantly differed in the severity levels of the three severity indicators. In conclusion, the WHOQOL-BREF is an appropriate health-related quality of life (HRQL) instrument for persons with TBI. Furthermore, the initial severity of the TBI might not be suitable for predicting levels of HRQL in persons with TBI.