Venous thromboembolism (VTE) is a major concern after total joint arthroplasty (TJA). We evaluated a risk-stratified prophylaxis protocol for patients undergoing TJA.A total of 2611 TJA patients were retrospectively studied. Patients treated with an aggressive VTE chemoprophylaxis protocol were compared with patients treated with a risk-stratified protocol utilizing aspirin and sequential pneumatic compression devices (SPCDs) for standard-risk patients and targeted anticoagulation for high-risk patients.We found equivalence in terms of VTE prevention between the 2 cohorts. There was a decrease in adverse events and readmissions among the risk-stratified cohort, although this did not reach statistical significance. A statistically significant reduction in costs (P < .001) was experienced with the use of aspirin/SPCDs compared with aggressive anticoagulation agents within the risk-stratified cohort.The use of aspirin/SPCDs in a risk-stratified TJA population is a safe and cost-effective method of VTE prophylaxis.