Background: Despite the improvement in the health care industry, the rates of undetected, untreated, and uncontrolled hypertension (HTN)are still very high, especially in rural areas of China.The aim of this study was to investigate the efficacy and efficiency of a guideline-based HTN management (novel therapy) in population of rural areas of Guangdong Province.Methods: Totally, 3113 patients with essential HTN in a rural area of Guangdong Province were enrolled and assigned to two groups,named traditional (n =372) and novel therapeutic (n =2741) groups, respectively.Patients in the traditional group were treated routinely,and patients in the novel group were treated in a novel model characterized by regular educational programs for hypertensive populations,close monitoring of blood pressure in combination with finely tuned antihypertensive medications, strict implementation of lifestyle modification and improving medical knowledge and skill of local medical staff efficiently.After 2 years of follow-up, primary endpoints including magnitude of systolic and diastolic blood pressures (SBP and DBP) decrease, treated and controlled rates, as well as secondary endpoints, were evaluated in both groups.Results: Initially, the treated rate was significantly higher in traditional group than that of novel group (71.15% vs.64.99%, P < 0.05),while the controlled rates were comparable and insignificant difference between baseline BP in both groups (31.07% vs.26.88%, P > 0.05).Four variables were significantly different, namely smoking rate, daily vegetable consumption (VC), and serum levels of low-density lipoprotein-cholesterol and fasting blood glucose between these two groups.After 2 years of follow-up, decreases in SBP and DBP were more prominent in the novel group (P < 0.001).Treated and controlled rates in both groups were both increased.Nevertheless, in comparison to the traditional group, controlled rate increased more significantly in the novel group (64.31% vs.37.85%, P < 0.001).Variables indicating lifestyle modification such as high sodium consumption, percentages of alcohol abuse, daily VC were profoundly improved in the novel group.Conclusions: The guideline-based HTN management implemented in the current study was beneficial for HTN control in rural areas of Guangdong Province.