Background: There is increasing interest in measuring quality of life (QOL) in clinical settings and in clinical trials. None of the commonly used QOL instruments has been validated for use postnatally. Aim: To assess the psychometric properties of the 26-item WHOQOL-BREF (short version of the World Health Organization Quality of Life assessment) among women following childbirth. Methods: Using a prospective cohort design, we recruited 320 women within the first few days of childbirth. At six weeks postpartum, participants were asked to complete the WHOQOL-BREF, the Edinburgh Postnatal Depression Index and the Australian Unity Wellbeing Index. Validation of the WHOQOL-BREF included an analysis of internal consistency, discriminate validity, convergent validity and an examination of the domain structure. Results: In all, 221 (69.1%) women returned their six-week questionnaire. All domains of the WHOQOL-BREF met reliability standards (alpha coefficient exceeding 0.70). The questionnaire discriminated well between known groups (depressed women and non-depressed women. P = 0.000) and demonstrated satisfactory correlations with the Australian Unity Wellbeing index (r = 0.45). The domain structure of the WHOQOL-BREF was also valid in this population of new mothers, with moderate-to-high correlation between individual items and the domain structure to which the items were originally assigned. Conclusion: The WHOQOL-BRF is a well-accepted and valid instrument in this population and may be used in postnatal clinical settings or for assessing intervention effects in research studies.