Objective To compare the efficiency and safety of rivaroxaban with those of warfarin in the treatment of acute venous thrombosis in the very old patients, in order to provide theoretical and clinical basis for the former’s application. Methods Eighty-two patients (81.5±5.6 years old) with ultrasonography-identified acute venous thrombosis in lower extremity treated in Chinese PLA General Hospital from March 2012 to March 2014 were enrolled in the study. They were randomized into rivaroxaban group (n=39) and warfarin group (n= 43). The rivaroxaban group was given low molecular weight heparin (enoxaparin, 1 mg/kg, subcutaneous injection, once per 12 h) and oral taking of 10 mg rivaroxaban, once per day for the first 3 days, and then followed by rivaroxaban alone at the same dose. The warfarin group was given warfarin plus above dose of low molecular weight heparin for the first several days until international normalized ratio (INR) stably ranged from 1.6 to 2.5, and then followed by oral warfarin with INR monitoring. All enrolled patients were followed up for 12 months. During that period, intravascular ultrasound examination (arteries and veins in upper and lower extremities), echocardiography, electrocardiography, chest and brain CT scanning, blood routine test, and blood biochemistry were carried out regularly, and hemoglobin, platelets, coagulation function, alanine aminotransferase （ALT） and serum creatinine （SCr） were measured at baseline, and 1, 3, 6 and 12 months respectively after treatment. Primary efficacy endpoint and safety endpoints were also observed and recorded. Results Thrombi all disappeared in both rivaroxaban and warfarin groups, and there were no recurrent or new venous thrombosis, pulmonary embolism and deaths in either group. At the 1st, 3rd, 6th and 12th months, the average INR was 201±051, 2.02±0.48, 205±052 and 203±055, separately in the rivaroxaban group, and was 1.98±0.44, 2.04±0.53, 2.03±0.49 and 201±0.46, respectively in the warfarin group. During the follow-up, no significant differences were seen in the efficiency and safety between the 2 groups. Hemoglobin, platelet, coagulation function, ALT and SCr had no significant changes in the 2 groups either. Conclusion Oral administration of rivaroxaban is an effective approach in the treatment of acute venous thrombosis in the very old patients. A dose of daily 10 mg is safety and effective for the treatment. Rivaroxaban has similar efficacy as warfarin, but is safer, more convenient to administer, as well as better compliance.