BACKGROUND: Current evidence might support the use of omega-3 fatty acids (preferably docosahexaenoic acid and eicosa-pentaenoic acid) for lowering blood pressure (BP), but the strength and shape of the dose-response relationship remains unclear. METHODS AND RESULTS: This study included randomized controlled trials published before May 7, 2021, that involved participants aged ≥18 years, and examined an association between omega-3 fatty acids (docosahexaenoic acid, eicosapentaenoic acid, or both) and BP. A random-effects 1-stage cubic spline regression model was used to predict the average dose-response association between daily omega-3 fatty acid intake and changes in BP. We also conducted stratified analyses to examine differences by prespecified subgroups. Seventy-one trials were included, involving 4973 individuals with a combined docosahexaenoic acid+eicosapentaenoic acid dose of 2.8 g/d (interquartile range, 1.3 g/d to 3.6 g/d). A nonlinear association was found overall or in most subgroups, depicted as J-shaped dose-response curves. The optimal intake in both systolic BP and diastolic BP reductions (mm Hg) were obtained by moderate doses between 2 g/d (systolic BP, −2.61 [95% CI, −3.57 to −1.65]; diastolic BP, −1.64 [95% CI, −2.29 to −0.99]) and 3 g/d (systolic BP, −2.61 [95% CI, −3.52 to −1.69]; diastolic BP, −1.80 [95% CI, −2.38 to −1.23]). Subgroup studies revealed stronger and approximately linear dose-response relations among hy-pertensive, hyperlipidemic, and older populations. CONCLUSIONS: This dose-response meta-analysis demonstrates that the optimal combined intake of omega-3 fatty acids for BP lowering is likely between 2 g/d and 3 g/d. Doses of omega-3 fatty acid intake above the recommended 3 g/d may be associated with additional benefits in lowering BP among groups at high risk for cardiovascular diseases.