Introduction: Hyperlipidemia is one of the most important and common risk factors of cardiovascular diseases especially Atherosclerosis and consequently CHD. Unalike age and gender, hyperlipidemia is a factor which can be controlled by altering the life style, nutritional habits and medical-medicinal interventions. Although serum level of cholesterol is always noticed in hyperlipidemia, hypertriglyceridemia, too, in addition to causing complications such as pancreatitis, has been known as one of the risk factors of cardiovascular diseases. Fibrates, after non-drug interventions, are the most used therapeutic category for treating hypertriglyceridemia. The objective of this study was to compare the effect of gemfibrozil and lopid on the serum level of triglyceride and total cholesterol. Method: The study was a cross-over study carried out on 53 hypertriglyceridemic patients (TG > 200mg/dl). At first basal triglyceride and total cholesterol levels were determined in all patients. Then Patients were randomly received either lopid or gemfibrozil with a dose of 300mg BD (before breakfast and dinner) for one month and after re-maesuring the total serum triglyceride and cholesterol, their drug was changed to the other and treatment continued for another one month. During the treatment period patients were observed for the adverse effects and serum levels of cholesterol and triglyceride were determined at the end of the treatment again. Data were analyzed by using repeated measure tests and through SPSS 11 software. Results: Mean basal triglycride and cholesterol levels were respectively 342.30±73.67mg/dl and 206.25±37.79mg/dl. While both drugs caused significant reduction in serum level of triglyceride (P<0.001), they had no significant effect on cholesterol level (P>0.05). There was no significant difference between the two drugs in regard to their effects on serum levels of triglyceride and total cholesterol (P>0.05). Conclusion: Considering the same efficacy, gemfibrozil can be used instead of lopid in hyperlipedemic patients.