This review investigates how the treatment of hypertriglyceridemia with fibric acid derivatives impacts lipid concentrations, lipid particle size, and the rate of cardiovascular events: expressly, to decide whether the use of fibric acid derivatives is an effective treatment option in the reduction of cardiovascular endpoints for patients with specific lipid parameters at baseline. Fibric acid derivatives reduce fasting triglyceride (TG) values by 15% to 50% (depending on baseline level) and low-density lipoprotein cholesterol (LDL-C) by 8%, and raise high-density lipoprotein cholesterol (HDL-C) by 9%. In conjunction with a statin, the amount of TG lowering is approximately doubled with the addition of the fibrate. When measured, fibrates decrease the TG concentration of very low-density lipoprotein cholesterol particles while increasing the TG content of LDL particles. The mean size of LDL particles increases and there is a substantial reduction in the number and proportion of small, dense LDL. In randomized trials in primary and secondary prevention populations, fibrates were associated with a significant reduction in nonfatal myocardial infarction in most studies. In the subgroup with elevated TG and/or depressed HDL-C at baseline, all trials have found statistically significant relative risk reductions of 27% to 65% in the primary cardiovascular endpoint of myocardial infarction and cardiovascular death.