The incidence of symptomatic venous thromboembolism (VTE) has been reported in up to 10.9% of patients undergoing knee arthroscopy without chemoprohylaxis. The purpose of this study was to evaluate the effectiveness of a chemoprophylaxis protocol in patients undergoing knee arthroscopy. A retrospective review of prospectively enrolled patients in a new institutional VTE prophylaxis protocol identified all patients undergoing knee arthroscopy during a 5-year period. This risk-based chemoprophylaxis protocol was instituted based on the Caprini model: patients at more than minimal risk were prescribed enoxaparin 40 mg daily for 3 weeks, while all others were instructed to take aspirin 325 mg twice daily. The primary outcome measure was incidence of VTE within 60 days postoperatively. Demographic characteristics and other risk factors for VTE were also recorded, as well as any postoperative complications. Among the 1,276 knee arthroscopies, there were 26 VTE events (2.0%), including 23 with deep vein thrombosis (DVT), two pulmonary emboli (PE), and one patient with both DVT and PE. There were no deaths or complications requiring hospitalization or reoperation. The VTE diagnosis occurred at, on average, 9 days postoperatively. Patients in the high-risk group treated with enoxaparin had a lower VTE incidence (1.49%) than those instructed to take aspirin (2.0%); = 0.75. Those undergoing an anterior cruciate ligament (ACL) reconstruction had the highest VTE incidence (2.87%). This study found that a chemoprophylaxis protocol with preferential use of aspirin or low-molecular weight heparin based on risk factors reduced the VTE incidence below to 2.0%, which is lower than most historical controls.Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.