Deep vein thrombosis (DVT) after arthroscopy has been considered a rare event; however, recent studies using ultrasound and venography have shown that the incidence of DVTs is underestimated. CASES:: This report describes 3 patients with DVT and/or PE after knee arthroscopy who were attributed to a genetic predisposition of hypercoagulability unknown to the patient and surgeon. CONCLUSIONS:: Genetic predisposition and autoimmune antibodies may play a role in the development of DVT after knee arthroscopy. We recommend focused questions regarding family history be added to the standard DVT/PE preoperative questionnaire.