OBJECTIVES: Pharmacotherapy costs represents huge burden for health institutions. The aim of the study is to compare prescribing practice and cost of outpatient hypertension pharmacotherapy between Bulgaria and Serbia. METHODS: A one year retrospective study from the point of view of the health system was performed, based on the collected reimbursed prescriptions with diagnosis AH (I10-I11) and for its complications - heart failure (I.50); sequelae of cerebrovascular disease (I.69); angina pectoris (I.20). Therapy was analysed according to the complexity (mono-, di-, etc.), frequency of prescribed medicines, reimbursed drug prices, and patient co-payment. To calculate the cost of the outpatient therapy was build a decision tree model matching the frequency of particular brand name prescribing, their prices, and complexity of therapy. RESULTS: The relative share of uncomplicated hypertension is comparable (67% in Serbia and 65% in Bulgaria). The ACE inhibitors are the first choice for hypertension treatment in both countries. Hypertension monotherapy differs significantly (47% in Bulgaria and 6% in Serbia), while di-therapy is comparable (35% and 30%). Among the complications prevails prescriptions for angine pectoris (70% in Serbia and 42% in Bulgaria) and heart failure (7% and 26%). The complications are usually treated with more than one medicine in Serbia while the monotherapy in Bulgaria is 66%. By including the cost and prevalence of mono-, di- etc therapy in the “decision tree” model we receive that the waged monthly cost of outpatient pharmacotherapy per patient with uncomplicated hypertension account for €12.56 in Serbia and €6.90 in Bulgaria. The total monthly cost of hypertension considering the chance of having complications is €13.39 in Serbia and €8.23 in Bulgaria. Patient co-payment in Bulgaria is higher. CONCLUSIONS: International cost comparisons are possible but depend on many external factors as regulatory and price control measures, prescribing habits, reimbursement policy.