OBJECTIVES: This systematic literature review (SLR) summarizes the published RWE for CDK4/6i, palbociclib, ribociclib, and abemaciclib, approved for the treatment of HR+/HER2- a/mBC. METHODS: An SLR was conducted to identify RWE studies on CDK4/6i treatment in HR+/HER2- a/mBC published since 2015. MEDLINE, Embase and Evidence-based Medicine Reviews databases were searched in July 2019. Relevant conference proceedings were searched from 2015-2019. RESULTS: 122 RWE studies were identified; 93/122 studies were only presented in conference posters/presentations. Most RWE studies were non-comparative and retrospective studies investigating palbociclib. Sample size ranged from 6-10,623 patients. In published research articles and abstracts, median progression-free survival (PFS) for palbociclib plus aromatase inhibitors (e.g., letrozole) and for palbociclib plus fulvestrant ranged from 13.3-24.5 and 11.6-15 months, respectively, in first line; 3.9-6.4 and 5.5-6.1 months, respectively, in second/later lines combined; and 4.5-8.9 and 5.5-13.3 months, respectively, in all lines combined. One comparative study presented PFS for palbociclib plus letrozole versus letrozole alone (20.0 vs. 12.1 months). Median PFS for abemaciclib monotherapy or plus endocrine therapy (ET) ranged from 3-7 months in second/later lines combined. One study reported median PFS of 5 months for ribociclib monotherapy or plus ET in second/later lines combined. Median overall survival (OS) reported for palbociclib treatment ranged from 21.1-24.5 months in all lines combined. A median OS of 44.9 months for first-line CDK4/6i (any) plus ET was reported in one study. CONCLUSIONS: This SLR provides a comprehensive summary of published RWE for CDK4/6i in HR+/HER2- a/mBC, providing insight into the impact of CDK4/6i in clinical practice. Most data are available from conference posters/presentations and from studies investigating palbociclib. Data are complementary to clinical trial data. While data suggest that CDK4/6i are associated with improved outcomes in HR+/HER2- a/mBC in a real-world setting versus the prior standard of endocrine monotherapy, studies with longer follow-up are needed.