The aim of the program was to study the tolerability of Tigerase® in patients with cystic fibrosis (CF) of all ages in rutine clinical practice. Study design: retrospective open uncontrolled comparative multicenter solid. Materials and methods of research: retrospective data of clinical observations were collected from medical records of patients with CF on the use of Tigerase®. Results: therapy with Tigerase® was well tolerated by 668 (93,4%) of 715 patients included in the study. In 47 (6,6%) patients, 127 adverse reactions (ADRs) associated with the use of Tigerase® were recorded. ADRs from the respiratory system were the most common. Of these, 24 (3,4%) were coughing and 10 (1,4%) had increased viscosity of bronchial secretion. Among all patients included in the study, the proportion of patients in whom ADRs were registered based on clinical manifestations (3,9%) did not differ statistically significantly from the proportion of patients in whom ADRs were recorded based on complaints only (2,8%) (p=0,30). The distribution of ADRs by the source of registration and place of residence of patients did not depend on their gender and age. Registration of ADRs in different regions of the country differed statistically significantly both in frequency and in the source of detection (p<0,001). ADRs were not recorded in several regions, and the largest number of ADRs were registered in patients living in Moscow, and most of them were based only on patient complaints. 22 patients (47% of the number of patients with ADR) had medical commissions for ADR, and only in 8 (17% of the number of patients with ADR) of them had expertise of specialists with experience in the treatment of patients with CF. In 29 patients (62% of the number of patients with ADR), the development of ADR did not require cessation of the Tigerase® therapy. Conclusion: in the majority of CF patients (93,4%) tolerated the Tigerase® therapy well.