The HYPEDIA study aimed at evaluating the implementation of the 2018 European guidelines for treating hypertension in primary care. A nationwide prospective non-interventional cross-sectional study was performed in consecutive untreated or treated hypertensives recruited mainly in primary care in Greece. Participants’ characteristics, office blood pressure (BP) (triplicate automated measurements, Microlife BPA3 PC) and treatment changes were recorded on a cloud platform. A total of 3,122 patients (mean age 64 ± 12.5 [SD] years, 52% males) were assessed by 181 doctors and 3 hospital centers. In 772 untreated hypertensives (25%), drug treatment was initiated in the majority, with monotherapy in 53.4%, two-drug combination in 36.3%, and three drugs in 10.3%. Angiotensin receptor blocker (ARB) monotherapy was initiated in 30%, ARB/calcium channel blocker (CCB) 20%, ARB/thiazide 8%, angiotensin converting enzyme inhibitor (ACEi)-based 19%. Of the combinations used, 97% were in single-pill. Among 977 treated hypertensives aged <65 years, 79% had BP ≥ 130/80 mmHg (systolic and/or diastolic), whereas among 1,373 aged ≥65 years, 66% had BP ≥ 140/80 mmHg. ARBs were used in 69% of treated hypertensives, CCBs 47%, ACEis 19%, diuretics 39%, beta-blockers 19%. Treatment modification was decided in 53% of treated hypertensives aged <65 years with BP ≥ 130/80 mmHg and in 62% of those ≥65 years with BP ≥ 140/80 mmHg. Renin-angiotensin system blocker-based therapy constitutes the basis of antihypertensive drug treatment in most patients in primary care, with wide use of single-pill combinations. In almost half of treated uncontrolled hypertensives, treatment was not intensified, suggesting suboptimal implementation of the guidelines and possible physician inertia.