Summary. Backgound: Over-investigation of low-risk patients with suspected pulmonary embolism (PE) represents a growing problem. The combination of gestalt estimate of low suspicion for PE, together with the PE rule-out criteria [PERC(−): age < 50 years, pulse < 100 beats min−1, SaO2 ≥ 95%, no hemoptysis, no estrogen use, no surgery/trauma requiring hospitalization within 4 weeks, no prior venous thromboembolism (VTE), and no unilateral leg swelling], may reduce speculative testing for PE. We hypothesized that low suspicion and PERC(−) would predict a post-test probability of VTE(+) or death below 2.0%. Methods: We enrolled outpatients with suspected PE in 13 emergency departments. Clinicians completed a 72-field, web-based data form at the time of test order. Low suspicion required a gestalt pretest probability estimate of <15%. The main outcome was the composite of image-proven VTE(+) or death from any cause within 45 days. Results: We enrolled 8138 patients, 85% of whom had a chief complaint of either dyspnea or chest pain. Clinicians reported a low suspicion for PE, together with PERC(−), in 1666 patients (20%). At initial testing and within 45 days, 561 patients (6.9%, 95% confidence interval 6.5–7.6) were VTE(+), and 56 others died. Among the low suspicion and PERC(−) patients, 15 were VTE(+) and one other patient died, yielding a false-negative rate of 16/1666 (1.0%, 0.6–1.6%). As a diagnostic test, low suspicion and PERC(−) had a sensitivity of 97.4% (95.8–98.5%) and a specificity of 21.9% (21.0–22.9%). Conclusions: The combination of gestalt estimate of low suspicion for PE and PERC(−) reduces the probability of VTE to below 2% in about 20% of outpatients with suspected PE.