Objective: To assess the clinical efficacy and safety profile of cardio selective beta blocker Bisoprolol (5 mg) and diuretic -hydrochlorthiazide (12.5 mg) in combination as monotherapy in patients with stage I essential hypertension. Study Design: Cross Sectional Study Place of Study: Medical OPD, Ghulam Mohammad Mahar Medical College Hospital, Sukkur Duration of Study: From January 2010 to July 2010 Material and methods: 120 patients (90 males and 30 females), in the age group of 30-65 years, newly diagnosed hypertensives with stage I essential HTN (Sitting SBP 140-159 and DBP > 90-99 mmHg, JNC VII report) attending the medical OPD of Ghulam Mohammad Mahar Medical College Hospital, Sukkur, from January 2010 to July 2010 were included for the study after obtaining written informed consent. All the cases were given tab. Bisoprolol 5 mg and Hydrochlorthiazide 12.5 mg in combination once daily as monotherapy in the morning and BP was recorded every week for 4 weeks in the supine and standing position. Results: The fall in BP (SBP and DBP) both in the supine and standing position at weekly intervals was significant (p < 0.05). BP was controlled in 80% of the cases. Side effects were reported in 5% patients in the form of weakness, lassitude, and muscle cramps. These side effects were mild in nature and did not warrant withdrawal of the study drug. Conclusion: Low dose of cardio selective?-blocker bisoprolol (5 mg) and diuretic - HCTZ (12.5 mg) provides greater additive effects with greater efficacy and tolerance, minimal side effects, and lower cost of therapy when used as monotherapy in case Stage I essential HTN.