In the current paper, we provide recommendations for the assessment of deep vein thromboses for the purpose of therapeutic trials evaluating antithrombotic drugs in the prevention of deep venous thrombosis. We have reviewed recently published articles on diagnostic and therapeutic studies, and we have evaluated methods of assessments. Ascending venography has been considered as the reference test for the confirmation of DVT. A roentgenographic image is subsequently available for review and allows classification by blinded, objective observers. However, venography poses substantial clinical and methodological limitations, particularly in the setting of systematic screening for all patients enrolled in a randomized clinical trial. Compression ultrasonography may replace venography for systematic screening of DVT in clinical trials, provided that specific methodological details are specified in the protocol and are fulfilled to ensure high and comparable sensitivity and specificity from all participating centers. This non-invasive technique has virtually no contraindications, and therefore more patients can be enrolled and evaluated. Furthermore, the compression ultrasonograph can be videotaped for central reading. Compression ultrasonography has already been adopted as the principal method for evaluating DVT in several ongoing large scale prevention trials with the approval of major drug agencies.