OBJECTIVES: To describe the impact of coronary artery bypass graft (CABG) surgery on health related quality of life (HRQOL) in post-menopausal women. DESIGN: Prospective cohort study. SETTING: Women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS). PARTICIPANTS: One hundred and thirty-seven women (mean age 66.6) who had CABG surgery while enrolled in HERS. MEASUREMENTS: Physical function was assessed using the 12-item Duke Activity Status Index (DASI), energy-fatigue with the four-item RAND scale, and mental health with the RAND mental health inventory each year. We defined baseline HRQOL from the interview that preceded the CABG (mean 4.6 months pre-CABG). To assess post-CABG HRQOL, we used the first interview that was obtained at least 6 months following the CABG (mean 11.5 months post-CABG). RESULTS: For all three measures of HRQOL, mean scores post-CABG were virtually identical to mean scores pre-CABG (mean pre and post scores were 20.8, 20.4 for physical function, 49.3, 49.2 for energy-fatigue, and 71.9 and 72.3 for mental health). After adjusting for demographic and clinical characteristics and the expected temporal change in HRQOL, differences between pre and post-operative HRQOL remained minimal. However, on an individual patient level, there was significant variability in HRQOL outcomes. For example, while mean physical function scores changed little, 32% of women were at least moderately better (scores improved by at least 0.5 standard deviations) following surgery, while 26% were at least moderately worse (scores declined by at least 0.5 standard deviations). CONCLUSION: Following CABG surgery in post-menopausal women, on average, HRQOL is virtually identical to the pre-operative baseline. However, there is significant variability, as substantial numbers of women are significantly better or significantly worse. © 2008 Society of General Internal Medicine.