Acute superior mesenteric venous thrombosis (ASMVT) is an intractable disease with poor prognosis. Argatroban, a direct thrombin inhibitor, may be a novel anticoagulant method in the therapy of ASMVT. The aim of the present study was to assess the efficacy and safety of early argatroban therapy in ASMVT patients. The current retrospective study reviewed a consecutive series of ASMVT patients receiving early argatroban therapy during hospitalization between March 2013 and April 2014, with 18 ASMVT patients included in the study. Of these, 16 patients without hepatic dysfunction underwent anticoagulant therapy with argatroban with a mean dose of 1.57±0.34 µg/kg/min and a mean duration of 12.2±3.7 days, while their activated partial thromboplastin time (aPTT) was elevated to 1.95±0.26 times the baseline value. In addition, 2 hepatic dysfunction patients received therapy with a dose of 0.41 µg/kg/min and 0.46 µg/kg/min, and with aPTT of 1.68 and 1.62 times the baseline value, respectively. Overall, 94% (n=17) of the patients presented clinical improvement, while 88% (n=16) of patients presented partially or completely dissolved thrombus in contrast-enhanced computed tomography images. The incidence of surgery and bowel resection was 6% (excluding 1 case with intestinal necrosis detected on admission). Furthermore, 11% (n=2) of patients experienced a bleeding episode, however no major bleeding or mortality occurred during hospitalization. During the follow-up, the mortality and the recurrence rate were 6% and 11%, respectively. In conclusion, early initiation of argatroban treatment may be an effective and safe therapy in ASMVT, manifesting efficient resolution of the thrombus, rapid improvement of symptoms, low incidence of bowel resection and bleeding complication, and low mortality rate.