BACKGROUND: There is a controversy regarding the investigation of patients with suspected acute pulmonary embolism (PE). AIMS: To compare the cost-effectiveness of alternative methods of diagnosing acute PE. Chest helical computed tomography (CT) alone and in combination with venous ultrasound (US) of legs and pulmonary angiography (PA) were compared to a conventional algorithm using ventilation-perfusion (V/Q) scintigraphy supplemented in selected cases by US and PA. METHODS: A decision-analytical model was constructed to model the costs and effects of the three diagnostic strategies in a hypothetical cohort of 1000 patients each. Transition probabilities were based on published data. Life years gained by each strategy were estimated from published mortality rates. Schedule fees were used to estimate costs. RESULTS: The V/Q protocol is both more expensive and more effective than CT alone resulting in 20.1 additional lives saved at a (discounted) cost of $940 per life year gained. An additional 2.5 lives can be saved if CT replaces V/Q scintigraphy in the diagnostic algorithm but at a cost of $23,905 per life year saved. CONCLUSIONS: The more effective diagnostic strategies are also more expensive. In patients with suspected PE, the incremental cost-effectiveness of the V/Q based strategy over CT alone is reasonable in comparison with other health interventions. The cost-effectiveness of the supplemented CT strategy is more questionable.