BACKGROUND In view of the controversies about the skewed X chromosome inactivation (XCI) and premature ovarian failure (POF) association, a meta-analysis of the published data was performed to evaluate the relationship between XCI skewing and POF. METHODS We searched for all published articles indexed in MEDLINE (1950 approximately 2009) and CNKI (1994 approximately 2009). Any case-control or cohort study that tested the association between skewed XCI and POF was included and data were extracted independently by two reviewers. We performed this meta-analysis involving 325 cases and 403 controls with Review Manager 4.2 software. RESULTS Four eligible studies were selected for meta-analysis. It suggested that there was no significant difference between the incidence of skewed XCI (XCI >or=70% skewing) in POF cases comparing to healthy controls, odds ratio (OR) = 1.13 [95% confidence interval (CI): 0.84 approximately 1.53, P = 0.42]. The link between extremely skewed XCI (XCI >or=90% skewing) and POF was also analysed, and no significant difference was found, either, OR = 1.46 (95% CI: 0.79 approximately 2.69, P = 0.22). CONCLUSIONS Skewed XCI had no association with POF. However, more case-control and cohort studies are needed in the future.