Background: Patients with a history of venous thromboembolism (VTE) undergoing total knee arthroplasty (TKA) are at a high risk of postoperative VTE. Purpose: In this high-risk population, we sought to evaluate the safety and efficacy of multimodal thromboprophylaxis. The regimen consisted of discontinuation of procoagulant medications, VTE risk stratification, regional anesthesia, rapid mobilization, perioperative use of pneumatic compression devices, vigorous ankle dorsiflexion during the recovery period, and chemoprophylaxis tailored to the patient's risk of VTE. Methods: We conducted a retrospective chart review of 141 consecutive patients with a history of VTE who underwent 177 elective TKA procedures between 2005 and 2019 by 2 arthroplasty surgeons at a single institution. The patients had a history of deep venous thrombosis (DVT) (n = 127; 72%), pulmonary embolism (PE) (n = 20; 11%), or both (n = 30; 17%). Postoperative chemoprophylaxis included aspirin (n = 20; 11%), anticoagulation (n = 135; 77%), or a combination of aspirin and anticoagulation (n = 21; 12%). Complications within 120 days, including VTE events, wound complications, bleeding, and unplanned readmissions, were recorded, as was 1-year mortality. Results: Five patients (2.8%) developed symptomatic DVT (3 distal, 2 proximal), and 4 patients (2.3%) developed symptomatic PE. The most common postdischarge complications were wound infection (n = 6; 3.4%) and stiffness requiring manipulation under anesthesia (n = 5; 2.8%). There was 1 emergency room visit and 13 unplanned readmissions; 3 patients developed intra-articular hematomas or prolonged wound drainage and recovered uneventfully. All patients were alive 1 year after surgery. Conclusion: The findings of this retrospective study suggest that multimodal prophylaxis may be safe and effective in patients with a history of VTE undergoing primary and revision TKA. More rigorous study is warranted.