The aim was to show that clinical assessment and serial Dopplers could be used to exclude deep venous thrombosis (DVT), and also that clinical assessment in combination with D-dimers could be used to exclude DVT. This was a prospective trial. Patients underwent clinical assessment, colour flow Doppler, and D-dimer measurement. Patients with an equivocal first Doppler and patients with a moderate/high pre-test clinical score had a repeat Doppler. Follow up information was obtained to see if further thromboembolism developed. Outcome measures included the reliability of the clinical assessment, Doppler, and D-dimer in excluding DVT. One hundred and ninety four patients were enrolled. The negative predictive value of a low medical pre-test score in excluding DVT was 92%. Eighty eight patients underwent D-dimer measurement. The negative predictive value of a D-dimer <400 units was 96%. The negative predictive value of a low clinical pre-test score and D-dimer <400 units was 100%. The negative predictive value of a low clinical pre-test score and D-dimer <800 units was 97%. The negative predictive value of the combination of a low clinical pre-test score and D-dimer <400 units was 100%. Twenty three per cent of patients had a low clinical pre-test score and D-dimer <400 units. Thus, a DVT could be excluded in 23% of referred patients. This information could be used to reduce Doppler requests by 23%. No patient in whom clinical assessment and serial Dopplers had excluded a DVT suffered further thromboembolism on follow up. This study has thus shown that a low medical pre-test score and negative Doppler reliably exclude DVT; a low pre-test score and negative D-dimer would reliably exclude DVT.