We compared three rapid d-dimer methods for the diagnosis of venous thromboembolism. Patients presenting to four teaching hospitals with the possible diagnosis of deep vein thrombosis or pulmonary embolism were investigated with a combination of clinical likelihood, d-dimer (SimpliRED) and initial non-invasive testing. Patients were assigned as being positive or negative for deep vein thrombosis or pulmonary embolism based on their three-month outcome and initial test results. The three d-dimer methods compared were: (a) Accuclot d-dimer (b) IL-Test d-dimer (c) SimpliRED d-dimer. Of 993 patients, 141 had objectively confirmed deep vein thrombosis or pulmonary embolism. The sensitivity of SimpliRED, Accuclot and IL-Test were 79, 90 and 87% respectively. All three d-dimer tests gave similar negative predictive values. The SimpliRED d-dimer was found to be less sensitive than the Accuclot or IL-Test. When combined with pre-test probability all three methods are probably acceptable for use in the diagnosis of venous thromboembolism.