Objectives: Existing efficacy trials of Omega-3 (w-3) fatty acids in mood disorders have yielded inconsistent results. The current paper is an effort to provide a systematic review and meta-analysis to evaluate efficacy of w-3 fatty acids in treatment of mood disorders. Design: We searched Medline, Embase, PsychInfo, and the Cochrane Controlled Trials registry up to June 2008 for randomized trials investigating efficacy of w-3 fatty acids in mood disorders. We conducted random effects meta-analyses. We used the I 2 statistic to quantify between-study inconsistency, and conducted pre-specified subgroup analyses to explore potential explanations for inconsistency. Observations: We included 21 trials in our systematic review and found 13 trials to be eligible for meta-analysis.The pooled standardized mean difference in depressed mood states (n = 554 in 12 trials) was 20.47 (95% CI: -0 . 92 , -0 . 02 ; I 2 = 82.7; p = 0.07) and in manic mood states (n = 126 in 4 trials) was 0.22 (95% CI: -0.21, 0.65; I 2 = 40.5; p = 0.31). We did not identify any treatment-subgroup interaction across forms of w-3 fatty acids preparations (P = 0.99) or patient diagnosis (bipolar vs. unipolar depressive disorder; P = 0.96); there was a significant correlation between w-3 fatty acids dose and treatment effect on depressive symptoms (r = 0.5, p = 0.04), but not on manic symptoms (P = 0.3). Conclusions: The available evidence suggests that w-3 fatty acids are a potential treatment of depressive disorders, but not mania.The unexplained between-study inconsistency and imprecision of the pooled estimates mitigate this suggestion. Large randomized placebo-controlled trials are needed to better estimate the value of this intervention for patients with depression. Copyright © 2009 by MedWorks Media Global, LLC. All rights reserved.