Certain algae contain the (n-3) fatty acid DHA, yet the relation between algal oil supplementation and cardiovascular disease risk factors has not been systematically examined. Our objective was to examine the relation between algal oil supplementation and cardiovascular disease risk factors. We conducted a systematic review of randomized controlled trials published between 1996 and 2011 examining the relation between algal oil supplementation and cardiovascular disease risk factors and performed a meta-analysis of the association between algal oil DHA supplementation and changes in the concentrations of TG, LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C). We identified 11 randomized controlled trials with 485 healthy participants that evaluated the relation between algal oil DHA supplementation and TG, LDL-C, and HDL-C. The median dose of algal DHA was 1.68 g/d. The pooled estimate for the change in TG concentration was -0.20 mmol/L (95% CI: -0.27 to -0.14), 0.23 mmol/L (95% CI: 0.16-0.30) for LDL-C, and 0.07 mmol/L (95% CI: 0.05-0.10) for HDL-C. DHA supplementation from algal oil, a marine source of (n-3) fatty acids not extracted from fish, may reduce serum TG and increase HDL-C and LDL-C in persons without coronary heart disease.