Angiotensin-converting enzyme (ACE) is an acid glycoprotein that converts angiotensin I into angiotensin II. It is produced mainly by activated alveolar macrophages and it resulted elevated in sarcoidosis patients. ACE is the only biomarker mentioned in WASOG international guidelines for the diagnosis and follow-up of sarcoidosis patients but its sensitivity and specificity are low. This study aimed to analyze serial measurements of ACE levels in sarcoidosis patients stratified according to concomitant ACE-inhibitor therapies (ACEIs). 136 serum samples from sarcoidosis patients were retrospectively enrolled in the study. Serial ACE concentrations were measured once year for each patient. Population were divided according to radiogical stages and ACEIs. ACE concentrations resulted higher in non-ACEIs than ACEIs group (p<E-04). This result was confirmed also stratifying population according to radiological stages particularly in stage 3 (p=2E-03) or stage 2 of the disease (p<1E-04). Considering ACEIs, serum ACE levels proved to be higher in sarcoidosis patients treated with zofenopril than in those treated with perindopril (p=2E-02), enalapril (p=2E-03) or ramipril (p=2E-04). Patients treated with ACEIs showed a progressive reduction in ACE levels to five years of follow-up (p=1.3E-02) and the zofenopril group recorded the highest ACE levels (p<1E-04). This retrospective study investigated changes in ACE levels in patients with sarcoidosis treated or not treated with ACEIs. Considering the overall low sensitivity and specificity of this biomarker, we suggest systematically investigating medical drugs prescribed for patients with sarcoidosis, in order to optimize the interpretation of ACE in clinical management.