Background/Aims: Previous studies have reported that fenofibrate therapy increases blood creatinine levels. The aim of this study was to evaluate the effect of fenofibrate therapy on the renal function in patients with hypertriglyceridemia and to determine the parameters associated with changes in renal functions. Methods: This prospective study enrolled 86 hypertriglyceridemic patients (triglycerides ≥ 200 mg/dL) who were divided into two groups: the fenofibrate group (n = 43), who received 160 mg of fenofibrate, and the control group (n = 43). Lipid profiles and renal function were measured at the beginning of the study and after 2 months. Results:The estimated glomerular filtration rate (eGFR) decreased in the fenofibrate group (p < 0.001), but did not change in the control group (p = 0.80). Accordingly, the decrease was more pronounced in the fenofibrate group than the control group (-18.6 ± 8.6 vs. 0.9 ± 9.6%, respectively; p < 0.001). Changes in serum creatinine (p < 0.001) and blood urea nitrogen (p < 0.005) levels were similar to those of eGFR. In a stepwise linear regression analysis, the percent change in creatinine was independently associated with fenofibrate therapy (r = 0.71; p < 0.001) and old age (r = 0.27; p < 0.05) in all patients. In the fenofibrate group, percent change in creatinine was associated with age (r = -0.51; p < 0.001) and smoking (r = 0.42; p < 0.005), while percent change was associated with body mass index (r = 0.31; p < 0.05) in the control group. Elevation of creatinine by 20% or more was associated with fenofibrate therapy (p < 0.001) and old age (p < 0.005) in all patients, and with old age (p < 0.001) in the fenofibrate group. Conclusions: Short-term fenofibrate therapy significantly impaired the renal function of hypertriglyceridemic patients, and this effect was more pronounced in elderly patients. This finding suggests that creatinine levels should be followed in patients receiving fenofibrate therapy.