Keeping in view the current scenario of increasing risk of dyslipidemia leading to coronary heart diseases in Indian population and dearth of conclusive evidences in support of homeopathy to treat dyslipidemia, we intended to evaluate the efficacy of empirically selected Dioscorea villosa 6CH in comparison with placebo. In this prospective, double-blind, randomized, parallel arm, placebo-controlled trial, 100 patients diagnosed with dyslipidemia were randomized in 1:1 ratio to one of the two interventions – Dioscorea villosa 6CH or identical looking placebo in the mutual context of lifestyle modification advices. The outcome measure was the blood lipid profile – triglyceride, total cholesterol (TC), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc), and high density lipoprotein cholesterol (HDLc), assessed at baseline, and 2 months after intervention. Comparative analysis was conducted on intention-to-treat basis to detect group differences using SPSS. The groups were comparable at baseline. After 2 months of intervention, pre-post comparison showed significant changes in triglyceride, total cholesterol and VLDLc in the verum group; and triglyceride, total cholesterol and LDLc in the placebo group; however, the group differences were non-significant; triglyceride (P=0.809), total cholesterol (P=0.316), HDLc (P=0.430), LDLc (P=0.192), and VLDLc (P=0.251). Per protocol analysis also revealed similar trends. Thus empirically selected Dioscorea villosa 6CH could not produce differentiable effect ct from placebo in treatment of dyslipidemia.