Objective: To compare the efficacy and safety of low-molecular-weight heparin and rivaroxaban in the prevention of thrombosis after total joint arthroplasty (TJA) based on a prospective cohort. Methods: A total of 280 adult patients scheduled for elective total hip arthroplasty or total knee arthroplasty were prospectively recruited and divided into two groups based on different intervention methods. The heparin group included 140 patients who were given subcutaneous injections of low-molecular-weight heparin after surgery. The rivaroxaban group included 140 patients who were given oral rivaroxaban after surgery. Both groups were treated for 21 days, and the efficacy and safety of thrombosis prevention were compared between the two groups. Results: The incidence rates of deep vein thrombosis (DVT) in the rivaroxaban group at 7, 14, and 21 days after surgery were lower than those in the heparin group (P<0.05). After treatment, the plasma fibrinogen (Fib) levels, the prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were longer than those before treatment (P<0.05), and the rivaroxaban group was longer than the heparin group (P<0.05). The whole blood low shear viscosity, whole blood medium shear viscosity, whole blood high shear viscosity, and endothelin-1 (ET-1) levels were all lower than those before treatment (P<0.05), and those in the rivaroxaban group were lower than those in the heparin group (P<0.05). The nitric oxide (NO) levels were higher than those before treatment, and the rivaroxaban group were higher than the heparin group (P<0.05). The incidence rates of bleeding and subcutaneous ecchymosis in the rivaroxaban group were lower than those in the heparin group (P<0.05), the proportion of the maximum subcutaneous ecchymosis area in the rivaroxaban group was lower than that in the heparin group (P <0.05). Conclusion: Rivaroxaban can better control the hemorheology of patients after TJA, improve vascular endothelial function, and regulate coagulation function indicators, thereby more effectively preventing postoperative thrombosis and is safer than low-molecular-weight heparin.