Background: Anemia is a common and unfortunate consequence of chemotherapy; patients receiving a variety of chemotherapy regimens often develop chemotherapy–induced anemia (CIA), which contributes to poor outcomes including increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Optimal therapy of CIA is controversial and involves the solitary and combined use of intravenous iron, red blood cell (RBC) transfusions, and erythropoietin stimulating agents (ESAs). Despite the baseline coagulopathies present in patients with malignancy, administration of both RBC transfusions and ESAs is associated with venous thromboembolism (VTE). It remains unknown whether the risk of VTE in patients with CIA is greater among patients who receive RBC transfusions or ESAs. Methods: A retrospective single-institution study analyzed 7360 patients with varying malignancies who developed CIA and received ESAs and RBC transfusion from 1998-2017. These patients were evaluated for subsequent development of VTE and categorized by prior receipt of RBC transfusion or ESA. Results: Among the 7360 patients with CIA, 5503 received either RBC transfusion or ESA and 1857 received both. Among all patients, 3466/7360 (47.1%) developed a VTE. The absolute risk of developing a VTE with receipt of a RBC transfusion was 0.38 compared to 0.19 with ESA. Patients with CIA who received RBC had twice the risk of developing a VTE compared with those who received ESA (p < 0.0001). Conclusions: While both RBC transfusion and ESA administration are independently associated with VTE, our data suggests a greater risk of VTE development with RBC transfusion as compared with ESA administration.