Background/ Objectives: There has been growing interest in using dietary intervention to improve the lipid profile. This work aims at analyzing the effects and the comparison of the enrichment of a diet with beta-glucans or rice bran in mildly hypercholesterolemic men. Subjects/Methods: The subjects initially consumed a 3-week Step 1 American Heart Association diet with rice bran-enriched foods. After this adaptation period, volunteers were randomly assigned to follow a crossover, controlled trial that consisted of two treatment with beta-glucan-or rice bran-enriched foods, each of 4 weeks, with a 3-week wash-out, like the adaptation period, between periods. Fasted blood samples were collected on days 0, 21, 49, 70 and 98 in both study arms for measuring low-density lipoprotein (LDL)-cholesterol (primary outcome), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B and glucose levels. Results: Twenty-four men (mean age: 50.3±5.3, mean body mass index: 24.9±1.9) completed the 14-week trial. Subjects in the 3-week adaptation period experienced significant reductions in the mean change of LDL cholesterol, total cholesterol, total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, apo A-I, apo A-I/apo B and glucose. During the intervention diet periods, a difference was found between treatment groups for the mean change in LDL (0.21 (95% confidence interval (CI): 0.02-0.40), P ¼ 0.033) and total cholesterol (0.34 (95% CI: 0.20-0.47), Po0.001). Other parameters evaluated were not significantly affected by the diet consumed. Conclusions: The results of the present crossover clinical trial showed that beta-glucan-enriched foods are more effective in lowering serum LDL levels, compared with rice bran-enriched foods.