Venous thromboembolism (VTE) is a cancer complication associated with poor survival. We have analyzed the prognostic impact of the development of a thrombotic episode in newly diagnosed multiple myeloma patients who received chemotherapy either with or without thalidomide on our Total Therapy 2 protocol. Of 668 patients enrolled, 155 developed VTE complication during treatment. The overall and event-free survival of patients who experienced VTE was not inferior. Of interest, we observed that patients who received intensive chemotherapy without thalidomide but developed a thrombosis experienced a significantly longer event-free survival compared with those without VTE (P = 0.02). Our observation suggests a possible beneficial effect of anticoagulation on survival in patients treated for myeloma.