Context: Seafood long-chain polyunsaturated omega-3 fatty acids (n-3PUFAs) improve insulin sensitivity in animal experiments, but findings remain inconsistent in humans. Adiponectin is a robust marker for insulin sensitivity and adipocyte function. Whether n-3 PUFAs affect adiponectin in humans is unknown. Objective: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the objective of the study was to perform a systematic review and meta-analysis of randomized, placebo-controlled clinical trials (RCTs) to determine the effect of n-3 PUFA consumption on circulating adiponectin in humans. Data Sources: MEDLINE, EMBASE, CABI (CAB abstracts), Cochrane Central Registry of Controlled Trials, ClinicalTrials.gov, SIGLE, and Faculty of 1000 were searched through to June 2012, supplemented with author contact and reference list searches. Study Selection: RCTs of either fish oil supplementation or isocaloric fish meal feeding that evaluated adiponectin as an outcome were selected for the study. Data Extraction: Two investigators independently extracted the data. Effect estimates were pooled using inverse-variance weighted, random-effects meta-analysis. Heterogeneity was assessed by the I2 and Q statistic. Prespecified sources of heterogeneity were investigated by meta-regression. Publication bias was assessed using funnel plots and Egger's test. Data Synthesis: Of 110 studies, 14 RCTs met inclusion criteria. Fourteen trial arms evaluated fish oil (fish oil, n = 682; placebo, n = 641). Fish oil increased adiponectin by 0.37 μg/mL [95% confidence interval (CI) 0.07; 0.67, P = .02]. Although effects in 11 of 14 trials were 0 or greater, statistical heterogeneity was evident (I2 = 72.9%), unexplained by n-3 PUFA dose or duration, study quality score, study location, or baseline body mass index (meta-regression P > .05 each). The funnel plot was asymmetric in favor of smaller trials with greater effects (Egger's P = .11); the fill-and-trim method suggested a theoretical pooled effect of 0.18 μg/mL (95% CI -0.15; -0.52, P = .28). Only 2 trial arms evaluated fish feeding (n = 136 intervention and 68 control subjects), for which the pooled effect on adiponectin was not statistically significant (-0.01 μg/mL, 95% CI -0.65; 0.64, P = 0.99), although CIs were broad due to the small number of subjects. Conclusions: In placebo-controlled RCTs, fish oil moderately increases circulating adiponectin, although with unexplained heterogeneity as well as potential publication bias. These findings provide no evidence for harm and support possible benefits of n-3 PUFA consumption on insulin sensitivity and adipocyte function. Copyright © 2013 by The Endocrine Society.