The aim of our study was to compare the diagnostic value of helical CT vs that of ventilation-perfusion (V/Q) scintigraphy as a first-line test in a diagnostic strategy in patients suspected of pulmonary embolism (PE). In a retrolective-prolective cohort study we tested the accuracy of helical CT vs V/Q scintigraphy in 123 patients suspected of PE. A diagnostic panel was asked to formulate the presumptive diagnosis on the presence or absence of PE, or of alternative disease by using two competing diagnostic strategies. These consisted of the patient history, laboratory tests and chest X-ray (together baseline tests) in combination with either helical CT or V/Q scintigraphy (CT strategy and V/Q strategy, respectively). The results were compared with the final diagnosis in each patient that was established from various reference tests (which included V/Q scintigraphy, pulmonary angiography and clinical follow-up). The CT and V/Q strategies were compared with regard to the accuracy for PE, for alternative diseases and with regard to the proportion of conclusive diagnoses that were made. The CT strategy was more accurate than the V/Q strategy for detecting or excluding PE. Sensitivity and specificity were 49 and 74 % for the V/Q strategy and 75 and 90 % for the CT strategy, respectively (P = 0.01). The CT strategy provided a conclusive diagnosis in a significantly larger proportion of patients than the V/Q strategy, 92 vs 72 % (P < 0.001). The CT strategy detected more alternative diagnosis than the V/Q strategy, 93 vs 51 %, respectively (P < 0.001). Helical CT seems more useful than V/Q scintigraphy as a first-line test in patients suspected of PE.