Background: The analysis of prescribing CDK4/6 inhibitors for patients with HR+/Her2neu- breast cancer was conducted at the St. Petersburg City Clinical Oncology Dispensary from April 2020 to October 2023. Patients in group 1 (n=365) received Palbociclib, and patients in group 2 (n=450) received Ribociclib. Methods: 99.45% of participants in the 1 group were female. In the 2 group all patients female. The average age of patients in both groups was 66 years. Results: In the first line of therapy, the clinical oncologist's choice more often leaned towards Ribociclib (p=0.0293). In later lines, Palbociclib was more frequently prescribed (p=0.0086). Ribociclib was significantly more often prescribed compared to Palbociclib in cases of primary hormone resistance (19.8%vs.13.9% (p=0.0288)). A higher "tumor burden" was documented at the start of therapy in patients receiving Ribociclib - 9.32% (5 or more loci of metastatic involvement). The frequency of overall response was significantly higher with Palbociclib (24.3%vs.11.7% (p=0.00001)), which is likely related to the higher incidence of primary hormone resistance and prescription in cases with a higher "tumor burden" in the Ribociclib group. The presence of PIK3CA mutations in patients of the Palbociclib group signifies a significant difference in response to therapy. The mPFS is 26(95% CI 16-29) when the mutation is present and 11(95% CI 9-14) when it is absent (p=0.0016). In the presence of metastatic liver impairment, significant differences in the mPFS assessment were in favor of Ribociclib (12 (95% CI 10-19) vs 11.0 (95% CI 9-15) (p<0.0001)). For the presence of a BRCA mutation, age, presence of bone metastases, brain metastases, visceral metastases (excluding liver), hormonal partner, there were no statistically significant differences between the groups for progression-free survival. The mPFS in both groups was comparable, and we didn't obtain statistically significant differences. In the 1st line the mPFS is not yet reached (p=0.602). In the 2nd line - in the Ribociclib group - 20, Palbociclib -22 (p=0.253). In the 3rd and later lines - the mPFS in the Ribocilib group - 19 (6.9-31.1), Palbociclib -14 (7.3-20.7) (p=0.775). The hematologic toxicity occurred significantly more often with Palbociclib (p=0.00001). As for Ribociclib, an undesirable event such as asthenia was prominent. The influence of dose-limiting toxicity on mPFS has been noted. In the presence of dose-limiting toxicity in the Palbociclib group, the mPFS has not been reached and is significantly different from the mPFS in patients who did not have a dose reduction. Conclusions: The analysis showed that Ribociclib is more often prescribed in the 1 line for patients with a higher 'tumor burden' and with primary hormone resistance. In relation to this, we observe a decrease in such an indicator as the frequency of overall response in this group of patients compared to Palbociclib.