Animal studies and small controlled studies in humans suggest that adiponectin may regulate blood pressure via brain-mediated and endothelium-mediated mechanisms. We performed a systematic review and meta-analysis to evaluate the epidemiological evidence on plasma adiponectin levels and hypertension in free-living adult population. A systematic search of MEDLINE and EMBASE, up to February 2013, identified 43 nonprospective and 5 prospective studies that included 17 598 adults (8220 with hypertension; mean age 19–69 years; and mean body mass index 22–38 kg/m ² ). Two investigators independently extracted data on adiponectin levels by hypertension status and dose–response relationship. We used a random-effects model to compute the weighted mean difference in adiponectin levels between adults with hypertension and normotensive adults and a 2-stage generalized least-square trend methods to compute the odds ratio of hypertension per 1 µg/mL increase in adiponectin. Adults with hypertension had 1.64 µg/mL (95% confidence interval, −2.07, −1.21) lower adiponectin levels than normotensive adults. Every 1 µg/mL increase in adiponectin levels was associated with 6% reduced risk of hypertension (95% confidence interval, 0.92, 0.97). These findings were consistent across study design and characteristics, including age, sex, and body mass index ( P >0.05). However, our meta-analysis was limited by unexplained large between-study heterogeneity, a small number of prospective studies, and selective reporting of dose–response data. In conclusion, epidemiological evidence suggests that plasma adiponectin level is a biomarker and possible mediator in the development of adiposity-related hypertension. The question remains as to adiponectin as a potential therapeutic target and its relationship with other adipokines in blood pressure regulation.