Objective To systematically review simple hypertension guidelines through methods as follows: (a) compare differences and similarities of the recommended drugs; (b) analyze differences of the recommended frequencies in different regions and quality levels; and (c) explore the recommended evidence basis, so as to better understand relevant guidelines. Methods Uncomplicated hypertension guidelines concerning pharmacological interventions were identified (terminated by March 2012) in Ovid, EMbase, Chinese Biomedical Disc (CBM) and WangFang database as well as guideline websites including NGC (National Guideline Clearinghouse), GIN(Guidelines International Network), NICE(National Institute for Health and Clinical Excellence) and CPGN (Clinical Practice Guideline Net, guidelines concerning pharmacological intervention in simple hypertension were included. A total of 6 domains (involving 23 items) in the Appraisal of Guidelines for Research and Evaluation (AGREE) were applied to assess the methodological quality of the guidelines. A comparative study was performed regarding the recommendations in guidelines from different regions as well as of different methodological qualities. Results A total of 27 guidelines concerning pharmacological intervention in simple hypertension were included, involving 6 continents, 13 counties, 3 regions and 3 international organizations. Publication dates ranged from 2003 to 2012. According to the AGREE instrument, 4, 17 and 6 guidelines were graded as Level A, B and C, respectively. There were only 2 domains, “Scope and Purpose” and “Clarity of Presentations”, getting high average scores (more than 60%) among all guidelines. The average scores of guidelines in different domains of AGREE varied with regions. There were 8 evidence-based guidelines which got higher average scores in each domain of AGREE than those of non-evidence-based guidelines. Guidelines varied with the standards of classifying ideal, normal, high normal blood pressure and hypertension. Diuretics were the first agent recommended by all guidelines, and the other recommendations were correlated with age and race. There was a tendency to recommend diuretics as basic drugs in two-drug combination therapy in North America, while calcium channel blockers (CCBs) were the most recommended agents in Asian guidelines. Conclusion The overall methodological quality of simple hypertension guidelines is suboptimal in different countries or regions. The 6 domains involving 23 items in AGREE vary with scores, while the scores of evidence-based guidelines are higher than those of non-evidence-based guidelines. There are differences in the standards of classifying ideal, normal, high normal blood pressure and hypertension. The first-line drug recommendations differ in regions and relate to age and race. Two-drug combination therapy regimens also vary with region.