Objectives: The aim of this research was to compare leading clinical guidelines for the treatment of hypertension with evidence from systematic reviews found in the Cochrane database. Material and methods: Using five theoretical clinical cases, a comparative treatment scheme for hypertension was developed according to the guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH), followed by the guidelines of the American Heart Association (AHA) and the American College of Cardiology (ACC), and systematic reviews from the Cochrane database: Pharmacotherapy for hypertension in adults aged 18 to 59 years, Pharmacotherapy for hypertension in adults 60 years or older, First-line drugs for hypertension. Results: The main differences between the guidelines are in the classification of blood pressure and the threshold values at which pharmacotherapy is initiated. Additionally, in cardiovascular risk assessment, ESC/ESH uses SCORE and SCORE-2OP tables as tools, while the ACC/AHA guidelines use the ASCVD calculator to assess the 10-year risk of cardiovascular events. Conclusion: The guidelines are fundamentally very similar when it comes to making pharmacological recommendations, whereas the Cochrane systematic reviews reveal significant differences. Unlike the Cochrane reviews, the guidelines allow more flexibility in adjusting therapy according to the specific needs of each individual patient.