Sequential diagnostic algorithms are used in the case of suspected pulmonary embolism (PE). The PEGeD study proposed a new diagnostic strategy to reduce the use of computed tomography pulmonary angiography (CTPA). We aimed to externally validate this diagnostic strategy in an independent cohort. We analyzed data from 3 prospective studies of outpatients with suspected PE. As per the PEGeD algorithm, patients were classified as having a low, moderate, or high clinical pretest probability (C-PTP). PE was excluded with a D-dimer <1000 ng/mL in case of low C-PTP and <500 ng/mL in case of moderate C-PTP. We assessed the yield and safety of this approach and compared them with those of previously validated algorithms. Among the 3308 evaluated patients, 1615 (49%) patients could have had PE excluded according to the PEGeD algorithm, without the need for imaging. Of these patients, 38 (2.3%; 95% confidence interval [CI], 1.7-3.2) were diagnosed with a symptomatic PE at initial testing or during the 3-month follow-up. On further analysis, 36 patients out of these 38 patients had a positive age-adjusted D-dimer. The risk of venous thromboembolic events among the 414 patients with a D-dimer <1000 ng/mL but above the age-adjusted D-dimer cut-off was 36 of 414 (8.7%; 95% CI, 6.4-11.8). We provide external validation of the PEGeD algorithm in an independent cohort. Compared with standard algorithms, the PEGeD decreased the number of CTPA examinations. However, caution is required in patients with a low C-PTP and a D-dimer <1000 ng/mL but above their age-adjusted D-dimer cut-off.