Prevention of deep vein thrombosis (DVT) is important in patients undergoing major orthopedic surgery. Although the detection of an elevated D-dimer level is useful for predicting DVT, it is not efficacious in postoperative patients being treated with anti-Xa agents. The soluble platelet glycoprotein VI (sGPVI) level is a marker of activated platelets, but not bleeding. Therefore, sGPVI levels are usually examined as a predictor of DVT in such patients. In the present study, 83 orthopedic patients were treated with 30 mg of edoxaban for prophylaxis of DVT. Fourteen patients developed DVT and 17 patients discontinued the prophylaxis due to decreased hemoglobin levels. Plasma levels of sGPVI in the patients were significantly higher after surgery than before surgery. On day 1, the sGPVI levels increased, while the platelet counts decreased. There were no significant differences in D-dimer, soluble fibrin, or FDP levels in orthopedic patients with and without DVT before surgery and on days 1, 4, and 8. Plasma sGPVI levels were significantly higher in the patients with DVT than in those without DVT on days 1 and 4. Plasma levels of D-dimer were significantly higher in patients with withdrawal than in those without. However, there were no significant differences in sGPVI levels between those with and without withdrawal. As D-dimer levels are known to increase in patients with withdrawal, this parameter is not useful for evaluating the risk of DVT in these patients. In contrast, the sGPVI level is not increased in those with withdrawal and may therefore be useful for evaluating the risk of DVT in postoperative patients treated with an anticoagulant.