Studies of adults presenting to the emergency department (ED) with acute pulmonary embolism (PE) suggest that those who are low risk on the PE Severity Index (classes I and II) can be managed safely without hospitalization. However, the impact of relative contraindications to home management on outcomes has not been described. To compare 5-day and 30-day adverse event rates among low-risk ED patients with acute PE without and with outpatient ineligibility criteria. We conducted a retrospective multicenter cohort study of adults presenting to the ED with acute low-risk PE between 2010 and 2012. We evaluated the association between outpatient treatment eligibility criteria based on a comprehensive list of relative contraindications and 5-day adverse events and 30-day outcomes, including major hemorrhage, recurrent venous thromboembolism, and all-cause mortality. Of 423 adults with acute low-risk PE, 271 (64.1%) had no relative contraindications to outpatient treatment (outpatient eligible), whereas 152 (35.9%) had at least one contraindication (outpatient ineligible). Relative contraindications were categorized as PE-related factors (n?=?112; 26.5%), comorbid illness (n?=?42; 9.9%), and psychosocial barriers (n?=?19; 4.5%). There were no 5-day events in the outpatient-eligible group (95% upper confidence limit, 1.7%) and two events (1.3%; 95% confidence interval [CI], 0.1-5.0%) in the outpatient-ineligible group (P?=?0.13). At 30 days, there were five events (two recurrent venous thromboemboli and three major bleeding events) in the outpatient-eligible group (1.8%; 95% CI, 0.7-4.4%) compared with nine in the ineligible group (5.9%; 95% CI, 2.7-10.9%; P?0.05). This difference remained significant when controlling for PE severity class. Nearly two-thirds of adults presenting to the ED with low-risk PE were potentially eligible for outpatient therapy. Relative contraindications to outpatient management were associated with an increased frequency of adverse events at 30 days among adults with low-risk PE.