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Omega-3 acid ethyl esters are the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), i.e., the ester part, attached at one end to an ethanol molecule - the ethyl part. These FDA-approved prescription products are used in combination with changes in diet to lower blood triglyceride levels in adults with severe (≥ 500 mg/dL) hypertriglyceridemia. This was the first fish oil-derived product to be approved for use as a drug. The first approvals came in Europe in 2001. The first approval in the US came in 2004. These prescription products have been tested in clinical trials. In the US, omega-3 ethyl esters are also manufactured and sold as dietary supplements.

Omega-3 acid ethyl esters are used in addition to changes in diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dL) hypertriglyceridemia. In the European markets and other major markets outside the US, omega-3 acid ethyl esters are indicated for hypertriglyceridemia as a monotherapy, or in combination with a statin for patients with mixed dyslipidemia and as secondary prevention after heart attack in addition to other standard therapy (e.g. statins, anticoagulants, beta-blockers, and ACE-I).

Intake of large doses (2.0 to 4.0 g/day) of long-chain omega-3 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater that 500 mg/dL). It appears that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglycerides, but DHA appears to raise LDL-C ("bad cholesterol") more than EPA, while DHA raises HDL-C ("good cholesterol") while EPA does not.

There are other omega-3 fish oil based prescription drugs on the market that have similar uses and mechanisms of action.

There are many fish oil dietary supplements on the market. There appears to be little difference in effect between dietary supplement and prescription forms of omega-3 fatty acids as to ability to lower triglycerides, but the ethyl ester products work less well when taken on an empty stomach or with a low-fat meal. The ingredients of dietary supplements are not as carefully controlled as prescription products and have not been tested in clinical trials as such drugs have.Prescription omega-3 products are more concentrated, requiring fewer softgels for the same daily dose.

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