Background: Despite the demonstrated success of multiple anticoagulation therapies for post-operative prophylaxis of thromboembolic disease in lower extremity arthroplasties, each modality comes with a unique set of limitations. Thus, the ideal anticoagulation medication which provides adequate therapy with minimal cost, complications, or added patient work is yet to be defined. One promising novel thrombophylactic supplement is fish oil, as many preliminary clinical trials have demonstrated a protective effect of fish oil against thrombosis in multiple clinical settings. In addition, others have demonstrated synergistic effect when combined with aspirin. However, there are paucity of studies that compared combined aspirin and fish oil therapy for venous thromboembolism prophylaxis with other pharmacological agents, especially in the field of orthopaedics. Therefore, this study evaluated: (I) risk of post-operative deep vein thrombosis (DVT) and pulmonary embolism (PE), and (II) bleeding complications; among patients who had primary total knee arthroplasty (TKA) and received one of the following regimens: (i) 325 mg aspirin and mechanical pulsatile stocking; (ii) rivaroxaban; or (iii) 325 mg aspirin and 1,000 mg fish oil. and 95% confidence intervals (CIs), for thromboembolic and bleeding events were calculated and compared between the aspirin and fish oil cohort vs. aspirin and pulsatile stocking cohort, and aspirin and fish oil cohort vs. rivaroxaban cohort. A P value of <0.05 was used to determine statistical significance.Results: A total of 25 DVT events were recorded including 1 of 300 (0.33%) in the aspirin and fish oil cohort, 22 of 300 (7.33%) in the aspirin and pulsatile stocking cohort and 2 of 250 (0.8%) in the rivaroxaban cohort. When comparing ORs, patients who received aspirin and fish oil demonstrated significantly lower risk for thromboembolic events when compared to the aspirin and pulsatile stocking group (OR: 0.045; 95% CI: 0.0061-0.3394; P<0.05). When compared to the rivaroxaban cohort the ORs did not differ significantly (OR: 0.416; 95% CI: 0.0376-4.6223; P>0.05). In addition, no PE events were recorded in any of the cohorts.When compared to rivaroxaban, the fish oil and aspirin cohort demonstrated significantly lower incidence Bonutti et al. Aspirin and fish oil for TKA VTED