End tidal carbon dioxide tension (P(ET,CO(2))) is a surrogate for dead space ventilation which may be useful in the evaluation of pulmonary embolism (PE). We aimed to define the optimal P(ET,CO(2)) level to exclude PE in patients evaluated for possible thromboembolism. 298 patients were enrolled over 6 months at a single academic centre. P(ET,CO(2)) was measured within 24 h of contrast-enhanced helical computed tomography, lower extremity duplex or ventilation/perfusion scan. Performance characteristics were measured by comparing test results with clinical diagnosis of PE. PE was diagnosed in 39 (13%) patients. Mean P( ET,CO(2)) in healthy volunteers did not differ from P( ET,CO(2)) in patients without PE (36.3+/-2.8 versus 35.5+/-6.8 mmHg). P(ET,CO(2 )) in patients with PE was 30.5+/-5.5 mmHg (p<0.001 versus patients without PE). A P(ET,CO(2)) of >or=36 mmHg had optimal sensitivity and specificity (87.2 and 53.0%, respectively) with a negative predictive value of 96.6% (95% CI 92.3-98.5). This increased to 97.6% (95% CI 93.2-99.) when combined with Wells score <4. A P(ET,CO(2)) of >or=36 mmHg may reliably exclude PE. Accuracy is augmented by combination with Wells score. P( ET,CO(2)) should be prospectively compared to D-dimer in accuracy and simplicity to exclude PE.