BackgroundThe incidence, risk factors, and outcomes of venous thromboembolism (VTE) in patients with chronic lymphocytic leukemia (CLL) and monoclonal B cell lymphocytosis (MBL) is not well described. ObjectivesWe aimed to determine the clinical characteristics, risk factors, and outcomes of incident VTE in patients with newly diagnosed MBL/CLL, and to compare the incidence to the age- and sex-matched general population. Patients/MethodsUsing the Mayo Clinic CLL Database, we identified 946 patients with newly diagnosed MBL/CLL between 1998–2021. Incidence of VTE was identified by querying the EHR for VTE-specific ICD-9 and ICD-10 codes and reviewing results of radiographic studies. ResultsEighty patients developed VTE. Incidence of VTE in patients with newly diagnosed MBL/CLL was ∼1% per year. In multivariable analyses, prior history of VTE (HR: 5.33, 95% CI: 1.93-14.68, P=0.001), and high/very-high-risk CLL-International Prognostic Index score (HR: 2.63, 95% CI: 1.31 – 5.26, P=0.006) were associated with an increased risk of VTE; receipt of CLL treatment or occurrence of non-hematologic malignancy was not. Development of VTE was associated with shorter overall survival (HR: 1.82, 95% CI: 1.30-2.55) after adjusting for age, sex, prior history of VTE, and Rai stage. Age- and sex-adjusted VTE incidence rate for patients with MBL/CLL and no prior history of VTE (n=904) was 1,254 per 100,000 person-years compared to 204 per 100,000 person-years in the general population, reflecting a 5.9-fold increase. Conclusions:Our study demonstrates a 6-fold increased risk of VTE in patients with MBL/CLL compared to the age- and sex-matched general population.