Background: VEN is an oral bioavailable BCL-2 inhibitor approved by the FDA in April 2016 for use in CLL. More data are needed to understand real world initiation, management and outcomes of CLL pts treated with VEN. Methods: This was a retrospective cohort study of CLL pts who initiated VEN. Investigators from 25 community centers provided pt-level data from medical records including demographics, clinical characteristics, ramp up management and outcomes. Tumor burden was assessed per FDA label, tumor lysis syndrome (TLS) was defined by Howard criteria and response was based on iwCLL criteria. The primary endpoint was response. Characteristics and outcomes were summarized by descriptive statistics. Results: 222 VEN pts were included, of whom 22% used VEN in combination with ibrutinib (7%) or an anti-CD20 (14%). Median age was 64 years (range 57-71); 82% had TP53 interruption ; 84% had ≥1 prior line of therapy (median 1; range 0-6); 62% had prior kinase inhibitor (KI) use; and 4% had prior use of 2 KIs. At baseline, 11%, 49% and 40% had low, medium and high tumor burden, respectively, and 27% initiated VEN as inpatient. During ramp up, 6% had a dose interruption; no dose modifications were reported due to hematologic abnormalities. TLS events occurred in 6% of pts (n = 13) with 2 pts experiencing clinical TLS, mainly among high risk pts. 34 pts (15%) discontinued VEN, mainly due to relapse (n = 5), refractoriness (n = 9), or in setting of disease response (n = 8). Maximum dose of 400mg was achieved in 53% of pts and 46% (n = 103) were maintained at doses < 400mg following ramp up. With a median follow up of 6.1 months, ORR was 75% (CR: 26%). Median time to best response was 3 months. Responses were not negatively affected by TLS or maintenance doses < 400mg. Among 38 pts assessed for minimal residual disease (MRD) during VEN, 23 (61%) were MRD negative. Resolution of baseline lymphadenopathy, lymphocytosis, or B symptoms were reported among 93%, 95%, and 96%, respectively. Conclusions: In this study, most VEN-treated CLL pts completed the ramp up, few experienced a TLS /hematologic event, and responses were comparable to clinical trials. Inpatient management deviated from the FDA label suggesting opportunity to improve adherence to initiation guidance.