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Background:Most patients with suspected pulmonary embolism (PE) have a positive D‐dimer test and undergo diagnostic imaging. Additional non‐invasive bedside tests are required to reduce the need for further diagnostic tests. Objectives:We aimed to determine whether a combination of clinical probability assessment and alveolar dead space fraction measurement can confirm or exclude PE in patients with an abnormal D‐dimer test. Methods:We assessed clinical probability of PE and alveolar dead space fraction in 270 consecutive in‐ and outpatients with suspected PE and positive D‐dimer. An alveolar dead space fraction < 0.15 was considered normal. PE was subsequently excluded or confirmed by venous compression ultrasonography, spiral computed tomography and a 3‐month follow‐up. Radiologists were unaware of the results of clinical probability and capnography. Results:PE was confirmed in 108 patients (40%). Capnography had a sensitivity of 68.5% (95% confidence interval [CI]: 58.9–77.1%) and a specificity of 81.5% (95% CI: 74.6–87.1%) for PE. Forty‐five patients (16.6%) had both a low clinical probability and normal capnography (sensitivity: 99.1%, 95% CI: 94.9–100%) and 34 patients (12.6%) had both a high clinical probability and abnormal capnography (specificity: 100%, 95% CI: 97.7–100%). Conclusion:Capnography alone does not exclude PE accurately. The combination of clinical probability and capnography accurately excludes or confirms PE and avoids further testing in up to 30% of patients.