Omega-3 polyunsaturated fatty acids like alpha-linolenic acid (ALA) may be beneficial for cardiovascular health. A cholesterol supplemented diet will increase ALA bioavailability. Conversely, drugs which inhibit intestinal cholesterol metabolism may also inhibit fatty acid absorption. Our study will determine if a cholesterol absorption inhibitor, ezetimibe, decreases circulating levels of ALA in humans. Patients were randomly assigned to one of four groups for a 6 weeks: 1) placebo; 2) ezetimibe therapy (10mg); 3) flaxseed oil (containing 1.0g ALA); or 4) ezetimibe and flaxseed oil supplementation. Flaxseed oil supplementation resulted in a significant increase in circulating ALA levels in patients who were not given ezetimibe. Ezetimibe significantly inhibited the ALA raising effects of flax oil. No significant differences in circulating lipids or cytokines between the treatments were observed. Thus, ezetimibe therapy inhibits the absorption of omega-3 fatty acids. Patients receiving ezetimibe therapy will not receive cardiovascular benefits from omega-3 fatty acids.