Background and Objectives There is limited information on the long-term efficacy and safety of olmesartan medoxomil in the management of hypertension in Chinese patients. We therefore conducted the present multicentre, single-arm, prospective, observational study to investigate the 24-week efficacy and safety of olmesartan medoxomil in patients with mild to moderate hypertension. Methods Eligible patients (diastolic blood pressure [BP] 90-109 mmHg and systolic BP <180 mmHg off antihypertensive medication) were started on olmesartan medoxomil 20 mg once daily, with the possible up-titration to 40 mg once daily during 24 weeks of follow-up, to control clinic BP to the target level (<140/90 and <130/80 mmHg in diabetes mellitus). In a subset of enrolled patients, 24-h ambulatory and home BP monitoring were also performed. Results In the intent-to-treat analysis (n = 348), at 24 weeks of follow-up, the mean +/- SD changes from baseline in clinic systolic/diastolic BP were 21.2 +/- 14.2/16.0 +/- 8.8 mmHg (p < 0.001). The proportions of patients who achieved the goal BP for systolic, diastolic and both were 81, 80 and 75 %, respectively. Olmesartan medoxomil also significantly (p < 0.001) reduced systolic/diastolic BP measured at patients' homes by 17.7 +/- 13.1/12.1 +/- 7.9 mmHg from baseline (n = 109), and reduced mean 24-h, daytime and night-time ambulatory BP by 13.3 +/- 16.3/7.6 +/- 9.5 mmHg, 13.9 +/- 17.4/8.0 +/- 10.4 mmHg and 12.3 +/- 18.1/6.8 +/- 10.2 mmHg, respectively (n = 87). Seven (2.0 %) serious adverse events were reported during follow-up. Conclusion In Chinese hypertensive patients, olmesartan medoxomil is efficacious in lowering BP as assessed by three different BP-measuring methods and has an acceptable long-term safety and tolerability profile.