Background: Bruton tyrosine kinase inhibitors (BTKis) are effective treatments for various B-cell malignancies including CLL/SLL but are known to be associated with increased bleeding risk. Current evidence indicating this association has largely been demonstrated in clinical trial research. However, bleeding risk in real-world CLL/SLL patients, who are often sicker with more comorbidities requiring anticoagulant (AC) or antiplatelet (AP) use is not well described. This study aimed to assess the prevalence of AC/AP use and explore risk factors for bleeding among real-world CLL/SLL patients receiving BTKi therapies. Methods: We conducted a retrospective cohort study using the claims-linked Premier PINC AI Healthcare Database of patients aged ≥18 years with a diagnosis of CLL/SLL from July 1, 2016 to March 31, 2022. Patients were followed from first BTKi prescription fill (index date) to earliest of BTKi discontinuation, death, or end of the study period. Patient comorbidities, treatments, and bleeding events were assessed using diagnosis and procedure codes and prescription claims. Multivariable-adjusted risk for bleeding events was assessed with Cox proportional-hazards regression. Results: Among 2091 patients with CLL/SLL receiving BTKi therapies, mean age was 65.7 years, 61.8% were men, and 77.7% were White. BTKi treatments included ibrutinib (86.3%), acalabrutinib (13.1%), and zanubrutinib (<1%). Overall, 4.3% of patients switched BTKis during follow-up; 615 (29.4%) had AC/AP use at any time during the study period, of whom 411 (66.8%) started after BTKi initiation. Bleeding events occurred in 526 (25.2%) patients during a mean BTKi exposure of 14.2 months, with an incidence of 26.6 per 100 person-years (PYs) overall, and 37.2 and 22.0 per 100 PYs in patients with and without any prescription AC/AP use, respectively. The proportion of patients with fatal bleeding was <0.3%. In adjusted models, risk of first bleeding event was higher for AC use (HR [95% CI] 2.33 [1.83–2.98]), age ≥65 years (1.32 [1.14–1.53]), women (1.28 [1.10–1.48]), and history (during 90 days prior to BTKi start) of bleeding (2.27 [1.87–2.76]), ulcers (2.21 [1.06–4.63]) or myocardial infarction (MI) (1.74 [1.31–2.33]) (all P≤0.05). Prescription AP use, race/ethnicity, and history of chronic kidney disease or thrombocytopenia were not statistically significant. Conclusions: In this large real-world study of bleeding risk in patients receiving BTKis, bleeding events occurred in 26.6 per 100 patients per year, with higher risk in AC users, women, and patients with history of bleeding, ulcers, or MI. However, the risk of fatal bleeding was low.