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Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea syndrome (OSAS). However, the impact of CPAP on quality of life (QOL) is controversial. The aim of this study was to systematically review and determine whether CPAP improves QOL in patients with OSAS. We performed a comprehensive literature search to identify studies published between 1966 and 2007comparing values of CPAP with control. Weighted mean difference (WMD) was used to analyze the data. The pooled WMD was calculated by using a fixed or random-effect model. The outcomes for 1,256 patients from 16 studies, of whom 656 patients underwent CPAP and 600 were controls, were included. CPAP led to significant improvements in the Nottingham health profile part 2 (WMD = 1.657; 95% CI = 3.005, -0.308; p = 0.016), but there was no difference in other general QOL scores. Patients undergoing CPAP scored better in physical function (WMD = 3.457; 95% CI = 0.144, 6.771; p = 0.041), body pain (WMD = 4.017; 95% CI = -0.008, 8.042; p = 0.05), energy vitality (WMD = 6.984; 95% CI = 0.557, 13.411; p = 0.033) and physical component summary (PCS) (WMD = 2.040; 95% CI = 0.045, 4.035; p = 0.045) using the SF-36 tool. This meta-analysis shows that CPAP does not improve general QOL scores but does improve physical domains and vitality. Study design and QOL questionnaire tools are important to capture and evaluate information efficiently. However, generic QOL instruments may not be adequate in detecting important changes in quality of life in patients with OSAS.