Pulmonary embolism remains a challenging diagnostic problem. We developed a simple diagnostic strategy based on combination of assessment of the pretest probability with perfusion lung scan results to reduce the need for pulmonary angiography. We studied 390 consecutive patients (78% in-patients) with suspected pulmonary embolism. The pretest probability was rated low (<10%), intermediate (>10%, < or =50%), moderately high (>50%, < or =90%) or high (>90%) according to a structured clinical model. Perfusion lung scans were independently assigned to one of four categories: normal; near-normal; abnormal, suggestive of pulmonary embolism (wedge-shaped perfusion defects); abnormal, not suggestive of pulmonary embolism (perfusion defects other than wedge shaped). Pulmonary embolism was diagnosed in patients with abnormal scans suggestive of pulmonary embolism and moderately high or high pretest probability. Patients with normal or near-normal scans and those with abnormal scans not suggestive of pulmonary embolism and low pretest probability were deemed not to have pulmonary embolism. All other patients were allocated to pulmonary angiography. Patients in whom pulmonary embolism was excluded were left untreated. All patients were followed up for 1 year. Pulmonary embolism was diagnosed non-invasively in 132 patients (34%), and excluded in 191 (49%). Pulmonary angiography was required in 67 patients (17%). The prevalence of pulmonary embolism was 41% ( n=160). Patients in whom pulmonary embolism was excluded had a thrombo-embolic risk of 0.4% (95% confidence interval: 0.0%-2.8%). Our strategy permitted a non-invasive diagnosis or exclusion of pulmonary embolism in 83% of the cases (95% confidence interval: 79%-86%), and appeared to be safe.