Deep venous thrombosis (DVT) and pulmonary embolism (PE) are significant concerns following lower extremity arthroplasty. Many prevention protocols exist. This study investigates the rate of venous thromboembolic disease (DVT and PE) in 423 patients undergoing consecutive unicompartmental knee arthroplasties by two surgeons (A.V.L., K.R.B.) using a multimodal prophylactic strategy. Risk stratification by the medical consulting team determined appropriate anticoagulation level. Eighty-two percent (knees) were managed with an aspirin-based program, 8% with 2 weeks of low molecular weight heparin followed by aspirin, and 8% with warfarin. No patient experienced symptomatic DVT or PE. Radiographic investigations revealed no asymptomatic venous thromboembolic disease. A risk stratification and multimodal venous thromboembolic disease prevention program based on the efficacy and safety of aspirin may prove to be the safest, most effective method in patients undergoing unicompartmental knee arthroplasty. The minimally invasive nature and rapid recovery associated with unicompartmental knee arthroplasty may support approaching the procedure more as an arthroscopy than an arthroplasty in terms of venous thromboembolic disease prevention.