Abstract: Objective To evaluate lipid-lowering efficacy and safety of RYR Cholestin, or Monascus purpureus (Red Yeast) Rice, in Americans with moderate hypercholesterolemia. Methods This study was an open-label, self-control, and multi-center clinical trial. A total of 187 subjects were entered into this trial (serum LDL-Cholesterol 3.50~4.92 mmol/L,total cholesterol 5.18~7.25 mmol/L, male:female=116:71), of whom 162 completed the study. Subjects were placed on the NCEP Step I Diet throughout the study and RYR Cholestin (2.4 g/day) was administered for 8 weeks following initial 4-week diet control. Results Being on the diet alone for 4 weeks resulted in no significant changes in serum lipids. RYR Cholestin treatment for 8 weeks reduced serum total cholesterol, LDL-Cholesterol and triglycerides by 16.6%, 24.0%, and 25.2%, respectively, and increased HDL-Cholesterol by 14.3% (all P<0.001). There were 97.5% of patients having ≥ 10% improvement in at least one of lipid risk factors, and 79.0% having ≥ 20% improvement. Discontinuation of RYR Cholestin intervention for 14 d led to a return of serum lipids to baseline of pre-study. And 29 possible product-related mild adverse reactions were reported. Conclusion RYR Cholestin is well tolerated and effective in reducing total and LDL-Cholesterol, and triglycerides, as well as in increasing HDL-Cholesterol in hypercholesterolemic patients, but those indicators return to the beginning baseline when the treatment is discontinued.