Objectives Treatment guidelines for acute pulmonary embolism (PE) recommend risk-stratifying patients to assess PE severity, as those at higher risk should be considered for therapy in addition to standard anticoagulation to prevent right ventricular (RV) failure, which can cause hemodynamic collapse. The hypothesis was that 12-lead electrocardiography (ECG) can aid in this determination. The objective of this study was to measure the prognostic value of specific ECG findings (the Daniel score, which includes heart rate over 100 beats/min, presence of the S1Q3T3 pattern, incomplete and complete right bundle branch block [RBBB], and T wave inversion in leads V1–V4; plus ST elevation in lead aVR, and atrial fibrillation suggestive of RV strain from acute pulmonary hypertension), in patients with acute PE. Methods Studies were identified by a structured search of MEDLINE, PubMed, EMBASE, the Cochrane library, Google Scholar, Scopus, and bibliographies in October 2014. Case reports, non-English papers, and those that lacked either patient outcomes or ECG findings were excluded. Papers with evidence of a predefined reference standard for PE and the results of 12-lead ECG, stratified by outcome (hemodynamic collapse, defined as circulatory shock requiring vasopressors or mechanical ventilation, or in-hospital or death within 30 days) were included. Papers were assessed for selection and publication bias. The authors also assessed heterogeneity (I2) and calculated the odds ratios (OR) for each ECG sign from the random effects model if I2 > 24% and fixed effects if I2 < 25%. Funnel plots were used to examine for publication bias. Results Forty-five full-length studies of 8,209 patients were analyzed. The most frequent ECG signs found in patients with acute PE were tachycardia (38%), T wave inversion in lead V1 (38%), and ST elevation in lead aVR (36%). Ten studies with 3,007 patients were included for full analysis. Six ECG findings (heart rate > 100 beats/min, S1Q3T3, complete RBBB, inverted T waves in V1–V4, ST elevation in aVR, and atrial fibrillation) had likelihood and ORs with lower limit 95% confidence intervals above unity, suggesting them to be significant predictors of hemodynamic collapse and 30-day mortality. OR data showed no evidence of publication bias, but the proportions of patients with hemodynamic collapse or death and S1Q3T3 and RBBB tended to be higher in smaller studies. Patients who were outcome-negative had a significantly lower mean Daniel score (2.6, SD ±1.5) than patients with hemodynamic collapse (5.9 SD ±3.9; P = 0.039, ANOVA with Dunnett’s post-hoc), but not patients with all-cause 30-day mortality (4.9 SD ±3.3; P = 0.12). Conclusions This systematic review and meta-analysis revealed 10 studies, including 3,007 patients with acute PE, that demonstrate that six findings of RV strain on 12-lead ECG (heart rate > 100 beats/min., S1Q3T3, complete RBBB, inverted T waves in V1–V4, ST elevation in aVR, and atrial fibrillation) are associated with increased risk of circulatory shock and deat...