Omega-3 fatty acids, particularly icosapent ethyl (a purified form of eicosapentaenoic acid, EPA), have shown significant benefits in reducing cardiovascular (CV) events in patients with hypertriglyceridemia, especially those on statins. The REDUCE-IT trial demonstrated that 4 g/day of icosapent ethyl reduced the risk of CV events, including death, myocardial infarction (MI), stroke, and hospitalization for unstable angina, by 25% compared to a placebo. This benefit was observed in patients with CVD, diabetes, or CV risk factors, with triglyceride (TG) levels between 135–500 mg/dL. In contrast, trials with mixed EPA and DHA formulations, such as the STRENGTH trial, did not show significant CV event reduction, suggesting that the purified EPA formulation may be more effective. Omega-3 fatty acids, including EPA and DHA, lower TG levels through mechanisms such as reducing VLDL production and increasing lipoprotein lipase activity. However, their benefits extend beyond TG lowering, with potential anti-inflammatory, antioxidant, and antithrombotic effects. These pleiotropic effects may contribute to the reduction of atherosclerosis and CV events. Despite this, the effectiveness of omega-3 fatty acids in reducing CV events has been inconsistent across trials, possibly due to variations in formulation, dosage, and patient populations. Guidelines from the 2021 European Society of Cardiology (ESC), 2020 American Diabetes Association (ADA), and 2019 ESC recommend icosapent ethyl for patients with hypertriglyceridemia and CVD risk factors, particularly those with TG levels >135 mg/dL despite statin therapy. The drug is approved as an adjunct to statin therapy in patients with fasting or non-fasting TG >150 mg/dL and established CVD or diabetes with more than two CV risk factors. It is also recommended for patients with hypertriglyceridemia and CVD risk factors, regardless of LDL-C levels. While icosapent ethyl has shown significant benefits in reducing CV events, its use is associated with an increased risk of atrial fibrillation and atrial flutter. Therefore, it should be avoided in patients with poorly controlled atrial fibrillation. Additionally, dietary sources of omega-3 fatty acids, such as fish and plant-based sources, may offer some benefits, but fish oil supplements may not be as effective due to variability in quality and composition. Future research should focus on understanding the molecular mechanisms of icosapent ethyl's benefits and its implementation in real-world settings. The role of omega-3 fatty acids in CV event prevention remains an important area of investigation, with ongoing studies aiming to evaluate their effectiveness in specific populations and identify those who derive the most benefit.Omega-3 fatty acids, particularly icosapent ethyl (a purified form of eicosapentaenoic acid, EPA), have shown significant benefits in reducing cardiovascular (CV) events in patients with hypertriglyceridemia, especially those on statins. The REDUCE-IT trial demonstrated that 4 g/day of icosapent ethyl reduced the risk of CV events, including death, myocardial infarction (MI), stroke, and hospitalization for unstable angina, by 25% compared to a placebo. This benefit was observed in patients with CVD, diabetes, or CV risk factors, with triglyceride (TG) levels between 135–500 mg/dL. In contrast, trials with mixed EPA and DHA formulations, such as the STRENGTH trial, did not show significant CV event reduction, suggesting that the purified EPA formulation may be more effective. Omega-3 fatty acids, including EPA and DHA, lower TG levels through mechanisms such as reducing VLDL production and increasing lipoprotein lipase activity. However, their benefits extend beyond TG lowering, with potential anti-inflammatory, antioxidant, and antithrombotic effects. These pleiotropic effects may contribute to the reduction of atherosclerosis and CV events. Despite this, the effectiveness of omega-3 fatty acids in reducing CV events has been inconsistent across trials, possibly due to variations in formulation, dosage, and patient populations. Guidelines from the 2021 European Society of Cardiology (ESC), 2020 American Diabetes Association (ADA), and 2019 ESC recommend icosapent ethyl for patients with hypertriglyceridemia and CVD risk factors, particularly those with TG levels >135 mg/dL despite statin therapy. The drug is approved as an adjunct to statin therapy in patients with fasting or non-fasting TG >150 mg/dL and established CVD or diabetes with more than two CV risk factors. It is also recommended for patients with hypertriglyceridemia and CVD risk factors, regardless of LDL-C levels. While icosapent ethyl has shown significant benefits in reducing CV events, its use is associated with an increased risk of atrial fibrillation and atrial flutter. Therefore, it should be avoided in patients with poorly controlled atrial fibrillation. Additionally, dietary sources of omega-3 fatty acids, such as fish and plant-based sources, may offer some benefits, but fish oil supplements may not be as effective due to variability in quality and composition. Future research should focus on understanding the molecular mechanisms of icosapent ethyl's benefits and its implementation in real-world settings. The role of omega-3 fatty acids in CV event prevention remains an important area of investigation, with ongoing studies aiming to evaluate their effectiveness in specific populations and identify those who derive the most benefit.