OBJECTIVES: The goal is to calculate the pharmacotherapy cost and quality of life of Bulgarian patients with rare endocrine diseases. METHODS: An ambispective study among hospitalized patients with acromegaly and Cushing syndrome was conducted at the University Endocrinology Hospital for Active Treatment of, Sofia. A bottom up approach was applied to calculate the average monthly pharmacotherapy costs per person for the period 2015-2016. The quality-of-life survey was accessed through SF-36. Descriptive statistics, correlation analysis and non-parametric Mann-Whitney test were applied using STATISTICA Version 13. RESULTS: The total number of included patients with acromegaly was 22 and 5 with Cushing syndrome. The patients over 50 years of age prevail in both groups – 68% and 80%, respectively. The pharmacotherapy for patients with acromegaly includes Sandostatin (72%) and Sandostatin+Pegvisomant (13.6%). The average monthly costs for acromegaly patients are 2 351.42 BGN (SD=1943.06) whereas Pasireotide therapy costs 6 465.65 BGN, at the ex-change rate of 1BGN=1.95Euro. The average quality of life did not differ significantly (P = .065) between the acromegaly and Cushing syndrome groups – 54.77 (SD=16,885) vs. 34.76 (SD=12,229), respectively. The men with acromegaly have higher values for physiological functions in comparison with the women (80.48 vs. 43.06). Acromegaly patients have statistically significantly higher values for vitality, energy or fatigue (53.26 vs. 46.8) and for general health perception (54.54 vs. 37). A negative low correlation between average costs and the average quality of life for acromegaly patients was defined – the higher the costs, the lower the quality of life (r=-0.134). CONCLUSIONS: The quality of life for patients with rare endocrine diseases is low especially regarding vitality, energy or fatigue and general health. The direct medical costs are significant and negatively correlated with the quality of life.