Aim: To compare the effectiveness of the four major antihypertensive drugs currently prescribed in health care setting to further the potential for evidence based prescribing practices. Material and Methods: This study was conducted in Department of Pharmacology, ICARE Institute of Medical and Research & Dr. Bidhan Chandra Roy Hospital, Haldia, West Bengal, India, enalapril, amlodipine, and thiazide are the most commonly prescribed medications for essential stage I and stage II hypertension from their respective classes. A prospective, randomized, open label experimental study design was conducted over a period of one year in patients diagnosed with primary (essential) hypertension. Results: Over a period of one year, a total of 100 patients were screened with 100 randomized across four treatment groups (i.e. Amlodipine, Atenolol, Enalapril and Thiazide). Twenty-five patients in each treatment group completed the follow up and entered to analysis. The mean (SD) baseline heart rate was 80.4 with no difference in distribution (p = 0.80). There was a significance difference in reducing SBP between Amlodipine (0.002) and Atenolol (p = 0.002). But there was no significant difference between Thiazide and enalapril (P = 0.67) There was no a significant difference in reducing DBP between amlodipine and thiazide (P = 0.82), amlodipine and enalapril (P = 0.66). Conclusion: This study revealed that amongst the three drugs amlodipine followed by atenolol was found to be the most effective drug in reduction of systolic blood pressure. Thiazide and enalapril did not show a difference in reduction of mean blood pressure. Further, long term randomized trials are highly recommended to inform revision of hypertension treatment guidelines.