Background Few studies have compared change in the health-related quality of life (HRQL) following treatment of non-ST-elevation acute coronary syndrome (NSTE-ACS) with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study is to compare changes in HRQL six months after hospital discharge between NSTE-ACS patients who underwent either PCI or CABG. Methods HRQL was assessed using the Seattle angina questionnaire at admission and six months after discharge in 1012 consecutive patients with NSTE-ACS. To assess associations of PCI and CABG with HRQL changes, logistic regression models were constructed treating changes in the score of each dimension of the Seattle angina questionnaire as dependent variables. Results Although both the PCI and CABG groups experienced angina relief and other improvements at 6-month follow-up (P < 0.001), the CABG relative to PCI group showed more significant improvements in angina frequency (P = 0.044) and quality of life (P = 0.028). In multivariable logistic analysis, CABG also was an independent predictor for both improvement of angina frequency (OR: 1.62, 95%CI: 1.09-4.63, P = 0.042) and quality of life (OR: 2.04, 95%CI: 1.26-6.92, P = 0.038) relative to PCI. Conclusions In patients with NSTE-ACS, both PCI and CABG provide great improvement in disease-specific health status at six months, with that of CABG being more prominent in terms of angina frequency and quality of life.