Background: Although, amlodipine (AML) and hydrochlorothiazide (HCZ) are recommended to initiate therapy in hypertensive patients, it has not been properly evaluated whether AML or HCZ would demonstrate a better adverse events profile. Objective: To determine whether AML or HCZ would be preferable to initiate antihypertensive treatment in type 2 diabetic Nigerians by comparing the adverse events profiles of the 2 drugs. Methods: Forty male (M) and female (F) newly diagnosed hypertensive subjects with controlled type 2 diabetic mellitus (T2DM) aged 43-68 years were randomized to AML and HCZ treatment groups of 20 patients each (10 Ms, 10 Fs), and they were treated respectively, with AML 10mg and HCZ 25mg, both drugs being given once daily for 48 weeks. Body mass index (BMI) was calculated for each subject. Blood pressure (BP), heart rate (HR), 24h urine volume were assessed at baseline and at the end of weeks 1, 3, 6, 12, 24, 36, and 48. Adverse events profiles were also recorded from week 1 through 48. Results: The drugs significantly reduced BP, though the effect of AML was significantly greater compared to that of HCZ (P<0.01). Diuresis was significant in HCZ group (P<0.01). There were 48 adverse events (48.5%) in the AML group including weight loss and mild tachycardia. No patient had peripheral pedal edema. Fifty one events (51.5%) occurred in HCZ group, weight loss, mild tachycardia, polyuria and myalgia/cramps being the commonest as well as impotence and visual disturbance. Conclusion: Though the two drugs appeared to be well tolerated, AML demonstrated a better BP-lowering effect and adverse events profile. Drugs that ensure adequate BP control and have the lowest possible risk for adverse events like AML, should be preferably used in diabetic Nigerian patients with essential hypertension.