Objectives: The primary strategy against Deep Vein Thrombosis (DVT) in athletes is systemic anticoagulation, which aims to mitigate risks such as Pulmonary Embolism (PE), thrombus propagation, and recurrent venous thrombosis. Argatroban, a synthetic thrombin inhibitor that functions independently of antithrombin, is evaluated here for its effectiveness and safety in treating athletes with lower extremity DVT. Methods: A cohort of 189 athletes diagnosed with DVT based on clinical assessments and duplex ultrasonography results were enrolled and randomly assigned into three groups. Group A (n=63) received Low-Molecular-Weight Heparin (LMWH) via subcutaneous injection, Group B (n=63) was treated with Argatroban, and Group C (n=63) received a combination of LMWH and Argatroban. Results: Statistical analysis revealed significant differences within and around the thigh and calf regions by the 14th day between Group A and C, and Group B and C, with p-values less than 0.05. Further, comparisons from day 0 to day 14 showed significant differences in thrombus regression across all groups, with p-values less than 0.01 or 0.001. The chi-squared test indicated that Group C had a more favorable outcome in thrombus regression compared to Groups A and B. Notably, Argatroban treatment was associated with a lower risk of bleeding and higher efficiency in DVT management among athletes. Conclusions: Anticoagulation with Argatroban, alone or in combination with LMWH, offers a viable and potentially safer therapeutic option for athletes suffering from DVT. Its use could facilitate quicker recovery and return to training or competition, emphasizing its role in sports medicine where rapid and effective treatment is crucial.