Background: Hypertension is the commonest non-communicable disease and the leading cause of cardiovascular disease in the world. Antihypertensive therapy often produces plasma lipid and glucose derangements. This study, therefore, was designed to find antihypertensive combinations that do not adversely affect plasma lipid and glucose profiles. Method: 240 carefully selected hypertensive patients of both sexes aged between 35-64 years were divided into two groups A and B. Baseline values of systolic and diastolic blood pressure, fasting blood sugar, serum total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride and reduced glutathione (GSH) were recorded. Fixed dose combinations of valsartan 80mg +hydrochlorothiazide 12.5mg (Diovan-HCT) and atenolol 50mg +chlorthalidone 12.5mg ( Diovan-50) were administered orally once daily to group A and group B subjects respectively. Post-treatment values were recorded at the end of six weeks. Results: The valsartan+hydrochlorothiazide combination produced a statistically significant higher reduction in diastolic blood pressure, plasma LDL-C, HDL-C, and triglyceride and a minimal increase in fasting blood compared with atenolol + chlorthalidone combination (p = 0.0001 for all variables). Conclusion: Valsartan + hydrochlorothiazide combination produced a better control of diastolic blood pressure with a favourable effect on FBS, plasma total cholesterol, LDL-C, HDL-C, and GSH.