PURPOSE: Patients undergoing total knee arthroplasty (TKA) are at a high risk of thromboembolic events, which is higher in obese patients. Determining the appropriate prophylaxis for venous thromboembolism (VTE) in obese patients is challenging. Therefore, we aimed to compare the effects of low molecular weight heparin (LMWH) with aspirin (ASA) and their combination for the prevention of thromboembolic events after TKA in obese patients. METHODS: In a retrospective study, 245 obese patients with BMIs over 30 who underwent TKA were enroled. Eligible patients were divided into three groups: Group A was given LMWH sodium (Clexane®) for 14 days, Group B was given ASA for 14 days, and Group C was given LMWH sodium (Clexane®) for 5 days and then ASA twice daily for the days between 5 and 14 postoperatively. The primary outcome was the incidence of VTE within three months. Secondary outcomes included routine laboratory evaluations (PT, PTT, INR, Hb, Hct, platelets, BUN and Cr) and adverse effects of ASA and LMWH, such as bleeding, anaemia, thrombocytopenia, and gastrointestinal or neurological symptoms. RESULTS: Regarding the incidence of DVT and PTE, we did not observe significant differences between groups ( > 0.05). A total of seven symptomatic VTE was observed in six patients. We observed two cases with PE who were in the Clexane group. Moreover, five individuals had DVT in the follow-up: three cases in the Clexane group, one in the ASA group, and one in the ASA + Clexane group, which was not statistically significant ( > 0.05). There were no differences between groups regarding the risk of adverse events and complications. CONCLUSION: We found that ASA is not inferior to enoxaparin in reducing VTE after TKA in obese patients. Therefore, given ASA's low cost and greater convenience, it may be considered a reasonable alternative for extended VTE prophylaxis for TKA surgery in obese patients. LEVEL OF EVIDENCE: Level III.